Chapter 26. Skeletal Imaging
Skeletal Dysplasia
DEFINITION
Skeletal dysplasia (also known as osteochondrodysplasia) is a genetically diverse group of >450 disorders of the skeleton causing abnormal bone length, shape, and density, with varying degrees of disability.
INCIDENCE AND EPIDEMIOLOGY
• Incidence of skeletal dysplasia is approximately 2.4– 4.5:10,000 live births.
• The most common lethal skeletal dysplasia is thanatophoric dysplasia (35%), followed by osteogenesis imperfecta type II (25%) and achondrogenesis (7%); collectively, these account for nearly half of all diagnosed skeletal dysplasias.
• The most common nonlethal skeletal dysplasia is achondroplasia, representing approximately 10% of all skeletal dysplasias.
ETIOLOGY AND PATHOGENESIS
• Skeletal dysplasia results from heterogeneous genetic defects that affect embryonic limb development through abnormal
• Extracellular structural proteins
• Metabolic pathways
• Folding and degradation of macromolecules
• Hormone and signal transduction mechanisms
• Nuclear proteins and transcription factors
• Oncogenes and tumor suppressor genes
• RNA and DNA processing and metabolism
• Most genetic defects are autosomal recessive (AR) or de novo autosomal dominant (AD) mutations, which may be associated with advanced paternal age (e.g., single nucleotide substitution c.1138G>A in FGFR3 associated with achondroplasia).
DIAGNOSTIC FEATURES
• Assessment for skeletal dysplasia is warranted if measured femur length is short (>2 SD below mean) for gestational age (Figs. 26.1 and 26.2), any long bones appear angulated or bowed (Fig. 26.3; Video 26.1), or limbs subjectively appear short compared with the fetal foot or trunk (Fig. 26.4; Video 26.2).
• A systematic approach (Box 26.1)8,9 should be used to assess the fetus, with all long bone lengths compared with standard biometric tables (Table 26.1). A long bone calculator using a spreadsheet is available online to calculate long bone deviations from the mean.
• Skeletal dysplasias are classified by site of shortened bones (Fig. 26.5).
• Rhizomelia—proximal limb shortened (humerus, femur)
• Mesomelia—intermediate limb shortened (radius, ulna, tibia, fibula)
• Acromelia—distal limb shortened (hands, feet)
• Micromelia—entire limb shortened
Figure 26.1 Short extremities prompt further investigation. Biometric measurements of fetus at 26 weeks’ gestation revealed head and abdomen growth mildly accelerated, with extremities measuring nearly 1 month less than dates; this disparity worsened as pregnancy progressed, and heterozygous achondroplasia was diagnosed following birth.
Figure 26.2 Biometric measurements show extremely short bones. Biometric measurements of fetus at 21 weeks’ gestation revealed extremities measuring approximately 7–8 weeks less than dates; thanatophoric dysplasia was diagnosed in fetus.
Figure 26.3 Short bowed femur. Image at 18 weeks’ gestation shows markedly short femur, resembling a telephone receiver, in fetus with thanatophoric dysplasia type I.
Figure 26.4 Short-appearing distal lower extremity. Tibia and fibula in fetus at 15 weeks appear shorter than foot length, making skeletal dysplasia possible.
(Left)
Confirm gestational age based on last menstrual period or firsttrimester ultrasound.
Measurements
Record lengths of all long bones bilaterally: femur, humerus, radius, ulna, tibia, fibula, clavicle; measure foot length; assess size and shape of scapula
Measure circumference of head, abdomen, chest, and cardiac area
Measure thorax in sagittal plane; note contour for bell shape in coronal plane
Calculate ratios
Thoracic circumference-to-abdominal circumference, normal ≥0.8
Cardiac circumference-to-thoracic circumference, normal <0.6
Femur length-to-abdominal circumference, normal >0.16
Femur-to-foot length, normal ≥1.0
Note morphology of bones
Shape: straight, curved, fractures, absent; unilateral vs. bilatera
(Right)
Echodensity: normal vs. poorly mineralized
Appearance of metaphyseal segment: premature ossification, spikes, epiphyseal calcifications
Abnormal posturing: clubbing, arthrogryposis
Assess hands for number of digits, shape of phalanges, and short fingers: polydactyly, syndactyly, brachydactyly
Note shape and mineralization of cranium and vertebral bodies: macrocrania, cloverleaf skull; scoliosis, platyspondyly, sacral agenesis
Obtain fetal profile: frontal bossing, midface hypoplasia, hypoplastic/absent nasal bone, micrognathia; assess biorbital diameter in coronal plane (hypertelorism or hypotelorism)
Evaluate fetus for other congenital anomalies: hydrocephalus, heart defects, hydrops fetalis
Amniotic fluid assessment
Doppler imaging to rule out growth restriction
Additional 3D and/or MRI may be helpful for assessing face and spine
• Micromelia is further subdivided by measured bone length: mild (>2 SD, but <3 SD below mean) or severe (>3 SD below mean).
• Mineralization is assessed through sonographic echogenicity of bones.
• Normal bone is hyperechoic (brighter white) and produces acoustic shadowing.
• Poorly mineralized bone is less echogenic (lighter gray) with less shadowing and reveals underlying structures (e.g., brain) better than expected (Fig. 26.6); the poorly mineralized calvaria may be compressible with transducer pressure, distorting the normal outline (Fig. 26.7; Video 26.3).
Figure 26.5 Prenatal diagnosis of skeletal dysplasias. Diagnostic algorithm to guide prenatal diagnosis of skeletal dysplasias. (Modified from Spirt BA, et al. Prenatal sonographic evaluation of short-limbed dwarfism: an algorithmic approach. Radiographics. 1990;10:217.)
Figure 26.6 Poorly mineralized calvaria. Axial view shows decreased echogenicity of skull in hypophosphatasia. The intracranial anatomy is “seen too well.”
• Accurate prediction of lethality is an important goal of prenatal diagnosis; sonographic findings associated with lethal outcome include5,13
• Early severe micromelia (>3 SD below mean)
• Femur length-to-abdominal circumference ratio <0.16
• Thoracic circumference <5th percentile
• Thoracic circumference-to-abdominal circumference ratio <0.79 (“bell-shaped” chest) (Fig. 26.8; Videos 26.4 and 26.5)
• Cardiac circumference-to-thoracic circumference >0.60 (Video 26.6)
• Poor bone mineralization
• Hydrops fetalis
• Polyhydramnios at initial imaging suggests esophageal compression with small thorax (survival to discharge 27% versus 83%, P < .001)13
• Consider 3D ultrasound imaging for face (Fig. 26.9) and hand appearance.
• Prominent ultrasound findings and their associated conditions are presented in Box 26.2.
• MRI may be helpful in assessing cranial sutures, intracranial anatomy, and vertebral structures in suspected nonlethal skeletal dysplasias; 3D helical CT imaging has also been used to assess vertebral abnormalities, though its use should be limited due to risks associated with fetal radiation exposure.
• First-trimester ultrasound in patients at high risk for skeletal dysplasia (e.g., affected parent with AD disorder, both parents with skeletal dysplasia, known carrier status of AR disorder, prior affected fetus) can identify lethal skeletal dysplasias (e.g., thanatophoric dysplasia, osteogenesis imperfecta type II) by exhibiting small crown-rump length (CRL), short femur, poor mineralization, and/or increased nuchal thickness.
• Brief descriptions of common skeletal dysplasias and their associated gene defects are presented in Table 26.2; a comprehensive searchable genetic database containing 481 osteochondrodysplasias with over 2200 phenotypes is available at http://101.200.211.232/skeletongenetics/.
DIFFERENTIAL DIAGNOSIS
• Fetal growth restriction (FGR)
• Aneuploidy (e.g., trisomy 21, trisomy 18, trisomy 13)
• Constitutionally small fetus (i.e., hereditary, familial short stature, ethnic variations)
• Nongenetic limb reduction conditions
• Malformation—disordered tissue development resulting from early embryonic teratogen exposure (e.g., viral infection, radiation, medications, diabetes)
• Disruption—breakdown of normal tissue (e.g., amniotic band sequence, vascular accident)
• Deformation—distorted shape of normal tissue (e.g., clubfoot with prolonged premature rupture of membranes)
ASSOCIATED ANOMALIES
• Polyhydramnios
• Hydrops fetalis
• Nonskeletal anomalies (cardiac, CNS, urogenital, and facial anomalies)
Figure 26.6 Poorly mineralized calvaria. Axial view shows decreased echogenicity of skull in hypophosphatasia. The intracranial anatomy is “seen too well.”
Figure 26.7 Compressible calvarium. Poorly mineralized calvarium deforms with pressure from the ultrasound probe as in this 26-week fetus.
PROGNOSIS
• Prognosis depends on which skeletal dysplasia is suspected and/or diagnosed and associated anomalies.
• The most common skeletal dysplasias with lethal outcome are listed in Box 26.3.
• Long-term morbidity includes short stature with varying degrees of orthopedic complications, developmental delay, and learning disabilities.
• Long-term survivors of skeletal dysplasia may have shortened life span.
Figure 26.8 Undersized chest. Coronal (A) and sagittal (B) views show small bell-shaped chest with larger-size abdomen, suggestive of pulmonary hypoplasia, as often seen in lethal severe micromelia.
Figure 26.9 3D face imaging. 3D rendered images show a prominent forehead consistent with frontal bossing and midface hypoplasia seen in heterozygous achondroplasia.
Achondrogenesis
Hypophosphatasia
Osteogenesis imperfecta
MACROCEPHALY/CLOVERLEAF SKULL (SEE FIG. 26.10)
Achondroplasia
Achondrogenesis
Camptomelic dysplasia
Thanatophoric dysplasia
SMALL THORAX (SEE FIG. 26.11)
Achondrogenesis
Asphyxiating thoracic dysplasia
Camptomelic dysplasia
Hypophosphatasia
Osteogenesis imperfecta II
Short rib–polydactyly syndrome
Thanatophoric dysplasia
BOWING OF LONG BONES
Achondrogenesis
Camptomelic dysplasia
Diastrophic dwarfism
Ellis–van Creveld syndrome
Hypophosphatasia
Osteogenesis imperfecta
Short rib–polydactyly syndrome
Thanatophoric dysplasia
FRACTURES OF LONG BONES
Achondrogenesis
Hypophosphatasia
Osteogenesis imperfecta
Achondrogenesis I : Severe micromelia, poorly mineralized skull and spine, bowing and numerous fractures present, polyhydramnios, hydrops; lethal
Achondrogenesis II : Severe micromelia, poorly mineralized distal spine, normally mineralized calvaria, macrocephaly, short ribs, polyhydramnios, hydrops; lethal
Achondroplasia, heterozygous Rhizomelic shortening, frontal bossing with midface hypoplasia (Fig. 26.11), bowed femur, brachydactyly with trident hand (Fig. 26.12); most frequent form of nonlethal dwarfism
Achondroplasia, homozygous Appears similar to thanatophoric dysplasia type 1 (see below); lethal
Asphyxiating thoracic dysplasia (Jeune syndrome) Mild micromelia, narrow thorax with short horizontal ribs, pulmonary insufficiency, renal abnormalities; variably lethal
Camptomelic dysplasia Mild micromelia with bowed femur and tibia, macrocephaly with micrognathia, absent scapulae, clubfeet, polyhydramnios; lethal
Chondrodysplasia punctata Rhizomelic shortening, microcephaly with frontal bossing, micrognathia, epiphyseal calcifications, mental retardation, seizures; lethal <2 years
Diastrophic dysplasia Mild micromelia with thick short bones, kyphoscoliosis, “hitchhiker thumb,” clubfeet
Ellis–van Creveld syndrome Also known as chondroectodermal dysplasia; mild micromelia, narrow chest with underdeveloped ribs, heart defects, polydactyly; variably lethal
Hypophosphatasia Severe micromelia, small thorax with rib fractures, poorly mineralized skull and bones with numerous fractures, bowed femurs; lethal
Mesomelic dysplasia Group of syndromes exhibiting nonlethal mesomelic shortening but otherwise generally normal phenotype
Osteogenesis imperfecta II Severe micromelia, poorly mineralized skull, numerous fractures/ bowing (Fig. 26.13), beaded ribs, soft calvaria, platyspondyly, hydrops fetalis; lethal
Osteogenesis imperfecta III Mild micromelia with poorly minimalized skull and bones, numerous fractures (see Fig. 26.14) and bowing, normal-sized chest, kyphoscoliosis; not lethal
Short rib– polydactyly syndrome Severe micromelia, underdeveloped ribs and small chest with pulmonary hypoplasia, polydactyly; lethal
Thanatophoric dysplasia I Severe micromelia with “telephone receiver” femurs, macrocephaly with frontal bossing, hydrocephalus, platyspondyly, polyhydramnios; lethal
Thanatophoric dysplasia II Severe micromelia with cloverleaf (kleeblattschädel) skull (see Fig. 26.10), short ribs with narrow thorax, platyspondyly, polyhydramnios; lethal
Figure 26.10 Cloverleaf skull. Axial (A) and sagittal (B) views show abnormal cloverleaf skull with midface hypoplasia (arrow) and prominent occiput and parietal bones (arrowheads) seen in thanatophoric dysplasia type II.
ANTENATAL MANAGEMENT
• Amniocentesis with microarray or noninvasive prenatal testing (NIPT) should be considered for karyotype and molecular testing (see Table 26.2).
• Whole exome sequencing may become more generally available and offer further insight into gene mutation(s) associated with skeletal dysplasia.
• Cell-free fetal DNA (cffDNA) has been shown to detect FGFR2 and FGFR3 mutations using next-generation sequencing with 96% sensitivity (95% CI, 81%–99.3%) and 100% specificity (95% CI, 85%–100%).17
• Obtain thorough patient history9
• Maternal medical history (e.g., poorly controlled diabetes, systemic lupus erythematosus, myasthenia gravis, hypothyroidism)
• Maternal exposures (e.g., warfarin, phenytoin, methotrexate, alcohol)
• Refer for genetic counseling and to obtain detailed family history that may reveal other affected individuals, suggesting diagnosis and/or familial short stature.
• Consider termination for suspected lethal skeletal dysplasias (see Box 26.3).
• Serial ultrasound examinations to monitor fetal growth, amniotic fluid, and worsening fetal condition (e.g., hydrops fetalis)
• Continued normal progression in bone length (femur, humerus), although at a lower percentile, makes significant skeletal dysplasia less likely.13,18
• Worsening growth (i.e., lowering percentiles or increasing SD below mean) makes skeletal dysplasia more likely.
• Long bones of fetuses with severe micromyelia (likely lethal) exhibit little growth over time.
• Abnormal biometric ratios suggestive of lethality become more pronounced with advancing gestation.
• Fetal achondroplasia manifests with mild rhizomelic shortening early in pregnancy with progressive worsening of bone growth in third trimester.
• Fetal echocardiogram recommended to assess cardiac structure and function.
• Prenatal neonatology and genetics consultation to discuss postnatal management and prognosis.
Figure 26.11 Thoracic hypoplasia. Small chest (arrowheads) compared to fetal abdomen at 25 weeks in fetus with thanatophoric dysplasia. Note prominent forehead (frontal bossing) with midface hypoplasia (arrow).
Figure 26.12 Trident hand. Images show short, stubby fingers seen in heterozygous achondroplasia at 20 weeks’ gestation (A) and on neonatal radiograph (B). Note size of fingers compared with the head.
• If the patient herself has a skeletal dysplasia (e.g., achondroplasia), prenatal consultation should include obstetric, neonatal, and anesthesia management plans.
• Delivery in tertiary care facility is recommended.
• Cesarean delivery should be considered for skeletal dysplasias associated with bone fractures or poor mineralization (see Box 26.2) and/or if the patient herself has a skeletal dysplasia.
NEONATAL MANAGEMENT
• With lethal skeletal dysplasias, neonatal resuscitative efforts are not generally recommended.
• Comfort care and supportive measures may be appropriate to allow parents time to accept lethal nature of the anomaly.
• If termination or fetal/neonatal demise, offer autopsy
with DNA and radiographic analysis (Fig. 26.13) to further identify the skeletal dysplasia and to aid in genetic counseling for future pregnancies, if desired.
• Initial care of liveborn fetus should be focused on respiratory status, with attention to the trachea and larynx; need for highly aggressive ventilation due to respiratory insufficiency (e.g., small chest) may indicate a very poor prognosis for survival.
• Continuing diagnostic assessment
• Skeletal (Fig. 26.14), spinal (Fig. 26.15), and cranial radiographs
• Molecular testing
• Consultation with geneticist to help with formulating diagnosis and providing prognosis.
• UCLA International Skeletal Dysplasia Registry (ISDR), formally located at Cedars-Sinai, can be a useful resource in diagnosing less common or difficult skeletal dysplasia cases (https://www.uclahealth.org/ortho/isdr).
KEY POINTS
• Short femur and/or humerus (<5th percentile) on routine biometric measurements should prompt a long bone survey to rule out skeletal dysplasia
Figure 26.13 Autopsy radiograph. Stillborn fetus with osteogenesis imperfecta type II shows multiple fractures and platyspondyly.
Figure 26.14 Neonatal bone survey. X-ray images of neonatal extremities show multiple fractures in osteogenesis imperfecta type III.
• A systematic approach should be used to evaluate a fetus with suspected skeletal dysplasia.
• The most common skeletal dysplasias are lethal; when skeletal dysplasia is suspected, a primary goal is to determine lethality, which may alter management of the pregnancy and delivery.
• Some cases (e.g., achondroplasia) may not become evident until the third trimester.
Arthrogryposis and Polydactyly
DEFINITION
Arthrogryposis multiplex congenita (AMC) describes a finding of fixed joint contractures in two or more body areas resulting in limited joint movement and variable contractures. Arthrogryposis is a descriptive term of a physical characteristic, rather than a diagnosis, per se, associated with a heterogeneous group of musculoskeletal disorders. Polydactyly refers to supernumerary digits present in the hand and/or foot.
INCIDENCE AND EPIDEMIOLOGY
• Arthrogryposis occurs in approximately 1:3000 live births.20
• Polydactyly is present in 1:3000 live births with male-tofemale ratio of 2:121,22 and is classified into three types
• Postaxial or ulnar (85%)23—extra digit on ulnar or fibular side of distal extremity; 10 times more common in African Americans, occurring in 1:300 live births, and commonly bilateral24 (likely an autosomal dominant trait)21
• Type A—well formed digit with metacarpal present
• Type B—poorly formed digit connected via pedunculated stalk
• Preaxial or radial (13%)23—extra digit located on radial or tibial side of distal extremity24,25
• Type 1—Bifid distal phalanx
• Type 2—Complete duplication of the distal phalanx
• Type 3—Bifid proximal phalanx with duplicated distal phalanx
• Type 4—Complete duplication of the proximal and distal phalanges
• Type 5—Bifid first metacarpal with complete duplication of the proximal and distal phalanges
• Type 6—Complete duplication of the entire thumb ray (metacarpal and proximal/distal phalanges)
• Type 7—Triphalangeal
• Mesoaxial or central (2%)22,23—extranumerary middle digit(s)
ETIOLOGY AND PATHOGENESIS
• Arthrogryposis is caused by lack of fetal movement (akinesia) leading to abnormal periarticular connective tissue and inadequately stretched muscles and tendons with resultant low muscle mass and fibrosis26 resulting from several factors.19,27
• Intrinsic factors—anomalies of fetal development (neuromuscular disorders, skeletal dysplasia, aneuploidy)
• Extrinsic factors—compression from oligohydramnios, malpresentation, fibroids, müllerian anomalies of uterus (e.g., bicornuate uterus)
• Environmental factors—infection, teratogen exposure
• Polydactyly results from defective embryologic differentiation of the digits with mesodermal rays that persist beyond programmed cell death, producing an extra digit or bifid digits.21
• Gene mutations associated with nonsyndromic polydactyly include ZNF141, GLI3, MIPOL1, IQCE, PITX1, GLI1, and ZRS/SHH.22,25
DIAGNOSTIC FEATURES
• Arthrogryposis is seen as abnormal limb posturing that is fixed in an exaggerated flexed (Figs. 26.16–26.18; Videos 26.7 and 26.8) or extended (Fig. 26.19) position with persistent lack of movement and typically affects more than one joint.
• Hands are affected with arthrogryposis more often than feet and may appear tightly clenched throughout the ultrasound examination (Fig. 26.20; Video 26.9).22
• May be sonographically apparent in only 25% prior to 24 weeks (Video 26.10).28
Figure 26.15 Platyspondyly. Neonatal chest x-ray reveals flattened vertebral bodies with increased interspinous distance in heterozygous achondroplasia.
AchondrogenesisAchondroplasia (homozygous)
Camptomelic dysplasia (variable)
Chondrodysplasia punctata (variable)
Hypophosphatasia
Osteogenesis imperfecta type II
Short rib–polydactyly syndrome
Thanatophoric dysplasia
BOX 26.3 LETHAL SKELETAL DYSPLASIAS
• Polydactyly appears as an extra digit; the hand and/or foot should be examined in the outstretched open position with digits enumerated (Figs. 26.21 and 26.22; Videos 26.11 and 26.12).
• Polydactyly is more likely diagnosed in second half of pregnancy.29
• Sensitivity is better for detecting arthrogryposis (81%) compared with polydactyly (19%), but the specificity for both findings is >99%.29
• Consider 3D imaging (Fig. 26.23; Video 26.13) and/or MRI to aid in diagnosis.30
Figure 26.16 Abnormal wrist posturing. Image shows wrist is flexed at 90 degrees with hooking fingers (arrow). This posturing is referred to as the “waiter’s tip” position and is associated with amyoplasia.
Figure 26.17 Excessive leg crossing. 3D image of fetus with twisted appearance of lower extremities in an exaggerated crossed position and clubbed left foot.
Figure 26.18 Gross pathology of arthrogryposis. Cross-legged “tailor’s position” is typical of arthrogryposis. Note the left clubfoot (arrows). There is also webbing in the flexor surface of the knee joint.
Figure 26.19 Unnaturally extended arm posturing. Image shows elbow extended at 180 degrees; elbow remained extended throughout examination, consistent with amyoplasia. Note the hooked fingers.
DIFFERENTIAL DIAGNOSIS
• Temporary unusual posturing of hand or foot
• Amniotic band sequence
• Vascular disruption
• Skeletal dysplasias (e.g., absent radius) (Fig. 26.24)
ASSOCIATED ANOMALIES
• Arthrogryposis is an isolated finding in only one-third of cases29,31; it may be a component of >400 specific conditions27
• Amyoplasia, a primary myopathy, accounts for onethird of all cases of AMC28
• Other primary myopathies (myotonic dystrophy)
• Fetal neuromuscular disorders (spinal muscular atrophy, Pena-Shokeir syndrome, cerebro-oculofacial syndrome)
• Connective tissue disease (diastrophic dysplasia)
• Metabolic disorders (Gaucher disease, glycogen storage disease IV, Zellweger syndrome)
• Infection (rubella, coxsackievirus, enterovirus)
• Maternal myasthenia gravis (transplacental passage of acetylcholine receptor antibodies)
• Other syndromes (e.g., VACTERL association [vertebral
abnormality, anal atresia, cardiac defect, tracheoesophageal fistula, renal agenesis, and radial limb abnormality])
• Aneuploidy (e.g., trisomy 18)
• Other findings associated with arthrogryposis include micrognathia, intrauterine growth restriction (IUGR), absent stomach bubble, short limbs, hydrops fetalis, pulmonary hypoplasia
• Polyhydramnios (particularly with fetal akinesia)
• Polydactyly is an isolated finding (i.e., nonsyndromic polydactyly) in 85% of cases; syndromic polydactyly is more commonly seen in preaxial (20%) versus postaxial (12%) polydactyly.23,25
• Most common associated anomaly is another limb defect (e.g., syndactyly)
• Can be an inherited trait, the result of teratogen exposure (e.g., diabetic embryopathy, valproic acid), or a component of nearly 300 recognizable syndromes22,23
• Aneuploidy (trisomy 13, trisomy 21)
• Preaxial polydactyly imparts almost threefold higher risk of Down syndrome (P < .0001)23
• Meckel-Gruber syndrome
• Oral-facial-digital (OFD) syndrome
• Skeletal dysplasias (e.g., Ellis–van Creveld syndrome, short rib–polydactyly syndrome)
• VACTERL association
• Smith-Lemli-Opitz syndrome
• Esophageal atresia
• Diamond-Blackfan and Fanconi anemia
PROGNOSIS
• Prognosis of arthrogryposis and polydactyly depends on associated abnormalities and whether the finding is part of a syndrome.
• Perinatal morbidity and mortality related to isolated limb defects are low; poor prognosis with AMC if accompanying hydrops, nuchal edema, pulmonary hypoplasia, CNS malformations, scoliosis, and/or absent stomach filling.28,31
• Recurrence of limb deformity is common owing to periarticular fibrosis and thickened joint capsules.26
• Long-term outcomes with AMC32
• Able to walk independently >50%
• Scoliosis or lordosis 35%
• Difficulty opening jaw 16%
• Regular pain 75% (88% joint pain, 49% muscle pain)
HANDS
Figure 26.20 Clenched hands. Image at almost 22 weeks’ gestation (in same fetus in Fig. 26.17) shows unchanging closed hands with what appears to be overlapping digits in a fetus. Karyotype was normal.
Figure 26.21 Hand with polydactyly. Image of fetal hand with polydactyly shows fingers 1 through 6. Postaxial polydactyly was a family trait in this case.
• Undergraduate degree 63%, graduate degree 27% (2.5 times higher than US population)
• Quality of life comparable to the general US population
ANTENATAL MANAGEMENT
• Amniocentesis with microarray testing should be considered for karyotype and possible genetic testing, particularly if there are other associated CNS, cardiac, or renal anomalies present.28
• Consider fetal echocardiogram with arthrogryposis to assess cardiac structure and function.
• Consider toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes simplex (TORCH) testing if amniocentesis not performed. Consider Zika virus testing in endemic areas (e.g., Brazil, Paraguay, Bolivia), particularly if concomitant fetal microcephaly or brain abnormalities present.
• Serial ultrasound examinations with arthrogryposis to monitor fetal growth, thoracic development, and amniotic fluid.
• Prenatal genetic consultation to determine if syndrome likely.
• Prenatal orthopedic surgery consultation to discuss postnatal management and prognosis.
• Delivery in tertiary care facility recommended only if
other anomalies or syndromes are suspected.
• Cesarean delivery should be reserved for usual obstetric
indications (e.g., malpresentation, which often accompanies AMC); fractures may occur during birth with AMC even with cesarean due to osteopenia.30
NEONATAL MANAGEMENT
• Pulmonary hypoplasia and/or difficulty with airway access should be anticipated if there is global fetal akinesia, significant kyphoscoliosis, or suspected jaw involvement (e.g., micrognathia).
• Careful physical examination should be performed to assess for other anomalies, syndromes, or aneuploidy.
• Consultation with geneticist and pediatric orthopedics to establish diagnosis and plan treatment.
• Physical therapy should be initiated as soon as possible to improve range of motion in arthrogryposis cases.
Figure 26.22 Hand and foot with polydactyly. Images demonstrate polydactyly with six fingers (A) and six toes (B) readily apparent. Other sonographic findings included holoprosencephaly and a proboscis. Amniocentesis revealed trisomy 13.
FINGERS
Figure 26.23 Clenched hands. 3D view of clenched hands with overlapping digits, consistent with arthrogryposis; fetus was confirmed to have trisomy 18.
• Offer autopsy if termination or perinatal demise.
• Surgical ablation of rudimentary supernumerary digits may be accomplished by suture ligation, but well-formed extra digits may require orthopedic reconstructive surgery.
KEY POINTS
• Persistent exaggerated posturing of joints (flexed or extended) or atypical angulation of the extremities is suspicious for arthrogryposis.
• Although arthrogryposis can be isolated, it is commonly associated with other associated abnormalities and syndromes and should prompt detailed anatomic evaluation and further investigation as appropriate.
• Polydactyly is more likely to be an isolated finding, but associated abnormalities are more common with preaxial polydactyly compared with postaxial polydactyly.
Clubfoot
DEFINITION
Congenital clubfoot, also known as talipes equinovarus, is a malformation of the fetal ankle producing various abnormal posturing of the foot.
INCIDENCE AND EPIDEMIOLOGY
• Incidence of clubfoot is approximately 1–3:1000 live births; male-to-female ratio is 2:1.33,34
• Approximately two-thirds of cases are bilateral; one-third are unilateral.33,35
ETIOLOGY AND PATHOGENESIS
• Clubfoot etiology is multifactorial and can be congenital, syndromic, or positional.34
• Intrinsic disruption of the neuromuscular unit (brain, spinal cord, nerve, muscle) and unopposed muscle activity restricting the ankle in a distorted position.
• Extrinsic factors that restrict normal mobility of the lower extremities include oligohydramnios, malpresentation, leiomyomas, and multifetal crowding.
• Genetic factors have been implicated (25% of cases are familial), but the genetic mechanism is unclear.34
• Gene mutations associated with clubfoot include TBX4, PITX1, NAT2, RMB10, and HOXA, HOXC, and HOXD gene clusters.36,37,38
• Risk factors for clubfoot include positive family history of clubfoot (OR = 7.80; 95% CI, 4.04–15.04), selective serotonin reuptake inhibitor exposure (OR = 1.78; 95% CI, 1.34–2.37), maternal smoking (OR = 1.65; 95% CI, 1.54– 1.78), maternal body mass index ≥30 (OR = 1.46; 95% CI, 1.29–1.65), and gestational diabetes (OR = 1.40; 95% CI, 1.13–1.72).37
DIAGNOSTIC FEATURES
• Clubfoot deformity is diagnosed when both the tibia and the fibula are visualized in coronal plane with the metatarsals (Fig. 26.25; Video 26.14), five toes (Fig. 26.26; Video 26.15), or sole of the foot (Fig. 26.27; Video 26.16) visible in the same plane, persisting during the course of the ultrasound examination.
• The foot most often is seen as plantar flexed (equinus) + inverted medially (varus) = talipes equinovarus; however, other abnormal ankle posturing is possible.
• Approximately 80% of isolated cases of clubfoot are detected prenatally; false-positive rate for prenatal diagnosis of clubfoot is 30%, often associated with initial diagnosis in the third trimester and/or unilateral clubfoot.39
• 3D imaging may improve sensitivity and specificity when clubfoot is suspected on 2D imaging (Fig. 26.28).
DIFFERENTIAL DIAGNOSIS
• Transient positional finding in normal fetus, particularly in the third trimester
• Rocker bottom feet (Fig. 26.29)
• Arthrogryposis (Figs. 26.30 and 26.31)
Figure 26.24 Absent radius. (A) Sharply angulated wrist in fetus at 21 weeks’ gestation, consistent with absent radius. (B) Postnatal radiograph confirmed diagnosis of absent radius.
Figure 26.25 Clubfoot, metatarsal view. Image shows tibia and fibula seen in parallel with the metatarsals of the foot visible in the same image (arrows).
Figure 26.26 Clubfoot, toe view. Image shows toes of the foot at right angles to tibia and fibula in parallel.
Figure 26.27 Clubfoot, sole of foot. Image shows tibia and fibula of lower extremity with the sole of the foot in the same plane, consistent with clubfoot.
Figure 26.28 3D imaging of clubfoot. 3D image clearly shows right foot inverted medially (arrowheads). Contralateral ankle appears normal.
• Skeletal dysplasia
• Amniotic band sequence
• Ectrodactyly
ASSOCIATED ANOMALIES
• Clubfoot is an isolated finding (idiopathic) in approximately two-thirds of cases.33,36,38
• When clubfoot is diagnosed, a detailed anatomic survey of the fetus should be performed to rule out other congenital malformations.
• Other associated anomalies (complex clubfoot)35,40
• Open neural tube defects (ONTDs) (e.g., anencephaly, myelomeningocele, caudal regression) (Video 26.17)
• Neuromuscular disorders (e.g., arthrogryposis, akinesia sequence, myotonic dystrophy)
• Aneuploidy (up to 30% with other structural anomalies present, 4% if isolated); more likely if bilateral (Fig. 26.32; Video 26.18) versus unilateral clubfoot33,40,41
• Skeletal dysplasias (e.g., osteogenesis imperfecta, diastrophic dysplasia, Kniest dysplasia, spondyloepiphyseal dysplasia congenita)
• VACTERL association
• Genetic syndromes and other malformation sequences38
• Other anomalies including cardiovascular, genitourinary, gastrointestinal, and facial anomalies39
• Clubfoot is unlikely to be missed if other congenital abnormalities are identified.
PROGNOSIS
• Severity of clubfoot and potential need for corrective surgery are difficult to predict prenatally.
• Approximately 90% of cases of clubfoot are found postnatally to have structural defects requiring orthopedic treatment; 10% are positional defects requiring no postnatal treatment.33
Figure 26.29 Rocker bottom feet. Bilateral rocker bottom feet in fetus with Pena-Shokeir syndrome.
Figure 26.30 Plantarflexion with hyperextended knee. In this 22- week fetus, the ankle is held in fixed plantarflexion with a hyperextended knee. There were multiple other anomalies, including Dandy-Walker malformation, hypoplastic left heart, hemivertebrae, and hydronephrosis, likely representing VACTERL association.
Figure 26.31 Bilateral crossed clubfeet. Image shows crossed legs with clubfoot in an unnatural posture that did not change during examination. Persistently crossed legs can indicate arthrogryposis.
• Postnatal classification systems (Dimeglio or Pirani) are used to assess clubfoot severity with a point score based on physical findings.34
• Treatment generally consists of serial casting followed by foot abduction brace (Ponseti method) or daily stretching and taping, followed by splinting (French physiotherapy method)42; there is no significant difference in outcomes between the two treatment options, with approximately 40% requiring tendon release surgery, regardless of initial treatment.34,42
• Long-term prognosis of clubfoot depends on associated abnormalities and postnatal treatment; however, with appropriate treatment, excellent prognosis is expected for reasonably normal function with isolated clubfoot.
• Ankle strength and overall range of motion may be 15% lower compared to children born with normal ankles (P < .002).42
• Although additional findings may be uncovered following birth in up to 7% (95% CI, 3.4–11.7), these are generally not severe enough to alter the overall prognosis of the affected fetus.41
ANTENATAL MANAGEMENT
• Consider repeat ultrasound examinations to reassess for other associated anomalies to confirm the finding of clubfoot.
• 75% of cases of complex clubfoot are diagnosed at 18–24 weeks, with classification changing from idiopathic to complex clubfoot based on imaging later in pregnancy.35
• Consider amniocentesis with microarray testing or noninvasive prenatal testing (NIPT) for karyotype if additional anomalies are present; amniocentesis is not recommended in cases of isolated clubfoot.43
• Prenatal pediatric orthopedic consultation may be helpful to discuss postnatal management and prognosis.
• No change in routine obstetric management is necessary in isolated clubfoot.
• Delivery in tertiary care facility is advised in cases of complex clubfoot (i.e., additional malformations detected).
NEONATAL MANAGEMENT
• No changes in usual neonatal management are necessary.
• Neonate should be examined for additional malformations.43
• With isolated clubfoot, 90% will have no additional malformations identified at birth; with complex clubfoot, additional anomalies will be seen in 57% (P < .001).44
• Additional malformations that are identified typically do not affect long-term prognosis.
• Arrange for pediatric orthopedic follow-up.
KEY POINTS
• Clubfoot should be suspected when the plantar surface of the foot is visible in the same plane as the tibia and fibula.
• Although most cases of clubfoot are isolated, careful anatomic survey should be performed to rule out other associated abnormalities or syndromes.
• With appropriate postnatal treatment of isolated clubfoot (splinting/casting, with or without surgery), long-term normal function is expected.
Sacrococcygeal Teratoma and Sacral
Agenesis
DEFINITION
Sacrococcygeal teratoma (SCT) is a germ cell tumor extending from the presacral area. Sacral agenesis (caudal regression) is a lack of embryonic development of the sacrum and lower spine. Both conditions are examples of closed spinal dysraphism.
INCIDENCE AND EPIDEMIOLOGY
• SCT occurs in 1:40,000 live births with male-to-female ratio of 1:3. SCT is the most common neoplasm in fetuses.45,46
• Sacral agenesis incidence is 1–5:100,000 live births47; it is classically reported in approximately 3:1000 diabetic pregnancies.48
ETIOLOGY AND PATHOGENESIS
• SCT is caused by continued growth of pleuripotential somatic stem cells in Hensen node, producing a tumor composed of embryonic ectoderm, mesoderm, and endoderm tissue.45
• Etiology of sacral agenesis is not well understood, but it is thought to result from interrupted growth of pleuripotential somatic stem cells at the caudal eminence owing to an extrinsic teratogen (e.g., maternal hyperglycemia, pyrexia), disrupting distal neural tube, caudal mesenchyme, and hindgut formation.
Figure 26.32 Bilateral clubfoot. Image shows bilateral clubfoot with toes from each foot pointing medially. Bilateral clubfoot increases the risk of aneuploidy and/or genetic syndromes.
DIAGNOSTIC FEATURES
• Sacrococcygeal teratoma
• SCT appears as a mixed echogenic solid (Figs. 26.33 and 26.34) and/or cystic mass (Fig. 26.35; Videos 26.19 and 26.20) extending from the coccyx to and often beyond the perineum; SCT can be confined internally in the presacral area in 10% of cases (Fig. 26.36).
• SCT can be seen in late first trimester (Fig. 26.37; Videos 26.21 and 26.22).
• Color Doppler imaging of SCT may show high-volume, high-velocity flow (Fig. 26.38).46
• MRI is useful to determine extent of SCT intrapelvic extension (Figs. 26.39 and 26.40).
• American Academy of Pediatrics Surgical Section (AAPSS) SCT classification is presented in Table 26.3.50
• Primarily cystic SCTs with low vascularity are generally low risk; cyst can be drained to facilitate vaginal delivery or low transverse (as opposed to classical) cesarean.51
• Tumor volume-to-fetal weight ratio (TFR)52 is used to determine prognosis with more solid, highly vascularized SCTs, using the prolate ellipsoid formula to estimate tumor volume in centimeters, divided by estimated fetal weight (EFW) in grams.
TFR = [(tumor lenght × width × depth) (π / 6)] ÷ EFW
• Sacral agenesis
• Sacral agenesis appears as abruptly ending lower spine on sagittal imaging (Fig. 26.41), confirmed on axial view (Fig. 26.42; Videos 26.23 and 26.24).
Figure 26.33 Sacrococcygeal teratoma. Sagittal view at 24 weeks’ gestation shows mixed echogenic mass (arrows) emanating inferior to the intact sacrum (arrowheads), consistent with sacrococcygeal teratoma.
Figure 26.34 Sacrococcygeal teratoma. Axial views (same fetus as in Fig. 26.33) at 29 weeks’ gestation with sacrococcygeal teratoma measuring approximately 10 cm in diameter. Note mixed echotexture within the mass.
Figure 26.35 Cystic sacrococcygeal teratoma vascular flow. Sagittal view of male fetus shows predominantly cystic sacrococcygeal teratoma at the fetal perineum (arrows). The fetal spine was intact. Bl, Bladder.
SACRUM
Figure 26.36 Internal sacrococcygeal teratoma. Soft tissue mass (arrows) at 23 weeks is primarily internal and confined to area inferior to the sacrum (type IV). The mass measured 1.8 cm in maximum diameter but enlarged to 3.5 cm by term and had a more typical mixed echogenic appearance.
Figure 26.37 Sacrococcygeal teratoma, first trimester. Fetus at 12 weeks’ gestation with soft tissue mass extending inferior to rump, consistent with sacrococcygeal teratoma.
Figure 26.38 Cystic sacrococcygeal teratoma vascular flow. Doppler image of sacrococcygeal teratoma shows sacral artery (arrow) and vascular flow within the mass (arrowheads).
Figure 26.39 Cystic sacrococcygeal teratoma MRI imaging. MRI shows sacrococcygeal teratoma as primarily external mass with minimal pelvic involvement (type I); the fetal spine appears intact.
• 3D skeletal imaging (Fig. 26.43) and/or fetal MRI may be used to confirm diagnosis.
DIFFERENTIAL DIAGNOSIS
• Meningocele/meningomyelocele
• Currarino syndrome—triad of internal presacral mass (teratoma or anterior sacral meningocele), partial sacral agenesis, and anorectal malformation; an autosomal dominant disorder or acquired as a de novo gene mutation of HLXB9 gene on chromosome 7q3653,54
• Lipoma (Fig. 26.44)
• Sirenomelia (single or fused lower extremity, renal agenesis, oligohydramnios) (Fig. 26.45)48
• Vestigial tail (Video 26.25)
• Imperforate anus
• Amniotic band syndrome
• Bladder outlet obstruction
ASSOCIATED ANOMALIES
• Cardiac, gastrointestinal, and genitourinary anomalies may be present.
• Anomalies associated with SCT46
• Maternal alpha fetoprotein (AFP) may be elevated.
• Hydrops fetalis may develop as a result of high-output cardiac failure secondary to arteriovenous shunting within SCT mass.
• Polyhydramnios or oligohydramnios.
• Placentomegaly with hydrops.
• Genitourinary obstruction may produce hydronephrosis and/or hydroureter.45,54
• Highest risk of any associated anomaly is with type IV SCT (OR = 4.40; 95% CI, 2.07–9.26).54
• Anomalies associated with sacral agenesis48
• Lower extremities are hypoplastic, appearing “crosslegged” and clubbed or misshapen with little movement.
• Imperforate anus (60%), renal anomalies (50%), ambiguous genitalia (15%).49
• Normal or increased amniotic fluid.
• May be part of a syndrome
• VACTERL association
• OEIS complex (omphalocele, cloacal exstrophy, imperforate anus, spinal malformation)
• Cloacal exstrophy
PROGNOSIS
• Perinatal morbidity and mortality related to SCT
• Solid, highly vascularized tumors have worst prognosis (hydrops, intratumor hemorrhage, malignancy).55
• Survival with solid tumor is 45%.56
• Survival with cystic/mixed tumor is 73%.56
• Tumor size >10 cm or tumor with rapid growth (>150 cm3/week) has ≥50% perinatal mortality.56,57
• TFR predicts poor prognosis (hydrops fetalis, need for fetal intervention, intrauterine fetal demise [IUFD], neonatal demise).51,52
• Poor prognosis if TFR >0.12 at <24 weeks (RR = 4.7; P < .0001) or TFR ≥0.11 at <32 weeks (RR = 6.2; P < .0001).58
• TFR ≤0.12 predicts uncomplicated prenatal course.52,58
• Preterm delivery reduces survival to 25%.45
• Associated hydrops fetalis is almost always fatal.45,56
• In the absence of hydrops or polyhydramnios with SCT, >70% survival is expected.45
• Up to one-third of SCTs are malignant, necessitating excision and cisplatin-based chemotherapy, with risk of tumor recurrence 10%–20%; however, malignancy is unlikely with Currarino syndrome.53,59
• Increased maternal operative risks with TFR >0.12 at <24 weeks if open fetal surgery, EXIT procedure, or classical cesarean (general anesthesia, increased risk of blood loss, and need for cesarean delivery in future pregnancies).51 Intrapartum EXIT procedure to debulk the potentially highly vascular tumor is indicated for large sacrococcygeal teratomas with impending hydrops due to high-output cardiac failure, tumor hemorrhage, or nonreassuring fetal testing.59a
Figure 26.40 Internal sacrococcygeal teratoma MRI imaging. MRI of same fetus as in Fig. 26.36 confirms the soft tissue mass (arrows) confined to the infrasacral area.
Figure 26.41 Sacral agenesis. Fetus at 14 (A) and 17 (B) weeks’ gestation with abrupt termination of spine at lumbosacral region (arrowheads).
Sacral agenesis was diagnosed. The echolucent mass caudal to the defect likely represents accumulated fetal urine. The fetus, delivered at term, lived only a few hours. C, Cervical; T, thoracic.
• Long-term outcomes related to sacral agenesis
• Sacral agenesis results in significant orthopedic disability (similar to paraplegia), but mental function is typically preserved.47,48
• Sensation is preserved at up to three dermatome levels lower than functional motor control.47,49
• Stool and urinary incontinence with recurrent urinary tract infections.49
ANTENATAL MANAGEMENT
• Amniocentesis with microarray testing or noninvasive prenatal testing (NIPT) should be considered for karyotype.
• Though not common, SCT has been reported with trisomies 1, 3, 10, and 13.59b
• Sacral agenesis is more likely due to diabetic embryopathy, but Currarino syndrome (which includes sacral agenesis) is associated with HLXB9 gene mutation.59c
Figure 26.42 Sacral agenesis confirmation. In axial view of the fetal abdomen, the cord insertion can be seen anteriorly (arrow), but spine is not visible posteriorly (arrowheads), consistent with sacral agenesis.
SACRAL AREA
Figure 26.43 Caudal regression. 3D imaging at 25 weeks in patient with poor diabetes control in early pregnancy shows absent sacrum (arrowheads).
• Fetal echocardiogram is recommended to assess cardiac structure and function.
• Frequent ultrasound and color Doppler imaging in SCT to monitor fetal growth, amniotic fluid, and worsening fetal condition (e.g., hydrops fetalis).
• Fetal MRI to characterize intraabdominal extent of lesion and aid in planning postnatal management.
• Monitor maternal health in cases of SCT for development of preeclampsia or mirror syndrome, which should prompt delivery.46
• Fetal in utero surgery for SCT has been proposed, including laser or radiofrequency ablation of feeding vessels and open fetal surgical resection.51
• Fetal nonstress and/or biophysical profile testing twice weekly beginning at 32–34 weeks.
• Prenatal neonatology, pediatric surgery (for SCT), and pediatric orthopedics (for sacral agenesis) consultation to discuss postnatal management and prognosis.
• Delivery with confirmation of lung maturity, evidence of hydrops, or maternal compromise (preeclampsia or mirror syndrome).
• Delivery in tertiary care facility is recommended.
• Cesarean delivery should be performed with SCT to improve perinatal outcome, particularly if tumor mass is solid or >5 cm in diameter; ensure skin and uterine incisions are adequate to avoid trauma to SCT mass (consider vertical or classical incision).45,57
• Caution for risk of rupture and hemorrhage of SCT mass during delivery.
• Drainage of predominantly cystic SCT may facilitate vaginal delivery.
• Delivery with sacral agenesis often complicated by malpresentation necessitating cesarean delivery.
NEONATAL MANAGEMENT
• SCT tumor mass should be protected from trauma, torsion, and desiccation (Fig. 26.46).
• Neonatal imaging with CT or MRI to judge extent of SCT mass or sacral agenesis.
Figure 26.44 Caudal lipoma. Paramedian soft tissue mass measuring 2 cm in maximum diameter (calipers) at 27 weeks did not involve the sacrum, representing a benign lipoma that was surgically excised following birth.
Figure 26.45 Sirenomelia. 3D image at 14 weeks’ gestation shows hypoplastic tapering lower body (arrowheads) and fused lower limbs as a single lower extremity (arrow), consistent with sirenomelia.
• Surgical repair of SCT should be arranged as soon as possible, particularly if neonate is in high cardiac output state.
• Flat plate radiograph to confirm extent of sacral agenesis (Figs. 26.47 and 26.48).
• Pediatric surgery and pediatric orthopedics consultation.
KEY POINTS
• A solid/cystic mass extending from the coccyx area with an intact spine is strongly suggestive of sacrococcygeal teratoma.
• Fetuses with sacrococcygeal teratoma are at risk for developing hydrops fetalis owing to high-output cardiac failure; therefore close fetal surveillance is warranted.
• Cesarean delivery is recommended for fetuses with large solid or mixed sacrococcygeal teratomas.
• Preconception poorly controlled diabetes may increase risk of developing sacral agenesis (caudal regression).
• Fetal 3D skeletal imaging and/or fetal MRI may be helpful to confirm diagnosis of sacral agenesis.
Neural Tube Defect
DEFINITION
Open neural tube defect (ONTD) is an embryologic defect in formation of the posterior vertebral arches of the spine, exposing the neural elements.
INCIDENCE AND EPIDEMIOLOGY
• ONTD, also known as spina bifida or spinal dysraphism, occurs in approximately 1:1000 live births.60,61
ETIOLOGY AND PATHOGENESIS
• The embryonic neural tube is formed via neurulation, which involves shaping, folding, and midline fusion of the neural plate, and is typically complete by 25 days after conception. ONTD results from a defect in primary
Figure 26.46 Postnatal appearance. Neonate with sacrococcygeal teratoma following delivery. The mass measured approximately 15 cm in diameter and weighed 1 kg after excision.
Figure 26.47 Postnatal radiograph. Multiple spinal defects are seen in this neonatal x-ray, including hemivertebrae causing scoliosis (arrow) and absent sacrum (arrowheads).
Figure 26.48 Autopsy radiograph. Postmortem radiograph shows spine terminating at the L2 level (arrowheads), consistent with sacral agenesis.
neurulation with failed caudal fusion of the neural tube and related regional epithelial defect, leaving neural tissue exposed.62
• Risk factors for developing ONTD include prior affected pregnancy (3%–5% risk of recurrence), teratogen exposures (folate antagonists, e.g., valproic acid and carbamazepine; approximately 1%–2% risk), folic acid deficiency (<400 mcg/day, OR = 3.72; 95% CI, 1.77–7.81), pregestational diabetes (type 1 and type 2 DM; OR = 2.88; 95% CI, 1.79–4.65), periconceptional fever (≥101°F; OR = 2.4; 95% CI, 1.5–4.0), maternal obesity (body mass index [BMI] ≥30; OR = 1.79; 95% CI, 1.51–2.13), MTHFR mutations (677C>T gene mutation; OR = 1.34; 95% CI, 1.17–1.54).62-68
DIAGNOSTIC FEATURES
• Spine is routinely imaged in axial (transverse) and sagittal (longitudinal) planes; if ONTD is suspected, coronal (anterior-posterior) images should also be acquired.
• ONTD appears on sagittal imaging as a defect in the dorsal aspect of the spine, typically with an overlying cystic mass (Fig. 26.49; Videos 26.26 and 26.27), and splaying of the posterior vertebral elements (V- or U-shaped vertebrae) seen on axial (Fig. 26.50; Videos 26.28 and 26.29) and coronal views (Fig. 26.51; Video 26.30).
• ONTD is classified by appearance of tissues overlying the bony defect.
• Myelomeningocele—sac containing spinal cord or other neural elements
• Meningocele—sac containing only protruding meninges and cerebrospinal fluid
• Myeloschisis—wide splaying of the vertebral arch with no visible covering and neural tube completely exposed (Fig. 26.52; Video 26.31)
• Lesion level is defined as highest vertebral level at which dysraphism is visualized (Fig. 26.53).
• Most (>80%) ONTD defects are located in lumbosacral region of the spine, but they can be located anywhere in the spinal column, including the cervical spine (Fig. 26.54).69
• 3D and MRI may be helpful in determining lesion level and size of bony defect (segment span) (Figs. 26.55 and 26.56).70
Figure 26.49 Myelomeningocele, sagittal. Sagittal view at 20 weeks shows disruption in continuity of posterior spinal elements, with overlying mixed cystic mass (arrows), consistent with myelomeningocele.
Figure 26.50 Myelomeningocele, axial. Axial view of same patient in Fig. 26.49 shows widely splayed V-shaped posterior elements of the sacrum (arrow) with overlying cystic mass (arrowheads), consistent with open neural tube defect.
Figure 26.51 Myelomeningocele, coronal. Coronal view shows splayed
posterior sacral elements (arrowheads) with small midline defect.
Figure 26.52 Myeloschisis. Sagittal view shows defect in lumbosacral spine (arrowheads) without visible covering or cystic structure, consistent with a myeloschisis.
• During first-trimester nuchal translucency screening at 11–14 weeks, abnormal appearance of the posterior brain in the midsagittal plane (Fig. 26.57) indicates high risk of open spina bifida and should prompt early anatomy imaging at 15–16 weeks’ gestation.71
• Qualitative nonvisualization of echolucent brainstem (BS), fourth ventricle (also known as intracranial translucency [IT]), or cisterna magna;72 sensitivity for all qualitative assessment methods 76.5% (95% CI, 65%– 85%) and specificity 99.6% (95% CI, 98.6%–99.9%)71
• Quantitative brainstem-to-brainstem-to-occipital bone (BS-BSOB) ratio, >95th percentile for CRL (abnormal if >1)73; sensitivity for all quantitative assessment methods 84.5% (95% CI, 70.8%–92.5%) and specificity 96.3% (95% CI, 95.2%–97.1%)71
DIFFERENTIAL DIAGNOSIS
• Sacrococcygeal teratoma
• Lumbosacral lipoma
• Sirenomelia
Figure 26.53 Lesion level. Coronal view shows splaying of posterior elements in the sacral region (arrow). The vertebrae are numbered, based on T12 (ribs attached).
Figure 26.54 Cervicothoracic dysraphism. On 3D image, the head is oriented at the top of the picture, and the cervicothoracic spine is seen widely splayed (arrow).
Figure 26.55 Spinal dysraphism. 3D image shows splaying of posterior elements of the sacrum (arrowheads), consistent with an open neural tube defect.
• Limb–body stalk anomaly
• Amniotic band syndrome
ASSOCIATED ANOMALIES
• ONTD is associated with increased maternal serum alpha fetoprotein (AFP), although AFP can be normal if there is a skin-covered lesion (e.g., spina bifida occulta).
• Intracranial findings with ONTD are indirect ultrasound markers of ONTD61,74 (Fig. 26.58, Video 26.32 and 26.33).
• Chiari II malformation with effacement of the cisterna magna and caudal retraction of the cerebellum (banana sign) (50%–100%)
• Hypoplastic cerebellum (82%–96%)
• Bifrontal retraction or scalloping of the frontal bone (lemon sign) (53%–100%)
• Ventriculomegaly (atrial width ≥10 mm), likely in second and third trimesters 45%–89%)
• Dolichocephaly (53%)
• Microcephaly (HC <5th percentile, 71%)
• Aberrant corpus callosum development (70%–90%)70
• Scoliosis.
• Clubfeet typical.
• Aneuploidy in 10% (primarily trisomy 18, trisomy 13, triploidy).60
• Other anomalies (cardiac, urogenital, skeletal, craniofacial, neurologic) present in 15%–30% of euploid fetuses; higher incidence in aneuploid fetuses.60
• ONTD can be part of a syndrome (e.g., VATER syndrome [vertebral defects, imperforate anus, tracheoesophageal fistula, renal defects], VACTERL association).
PROGNOSIS
• Prognosis of ONTD depends on
• Level and size of lesion
• Associated anomalies
• Aneuploidy
• Ventriculomegaly
• Type of surgical closure
• In general terms, the larger and higher the lesion, the worse the prognosis for survival, motor function, and continence.
• Perinatal mortality related to isolated ONTD is approximately 10%–15%.69
Figure 26.56 Lumbosacral myeloschisis. 3D image at 32 weeks demonstrates absent posterior elements in the lumbosacral area (arrow), without overlying cystic mass, consistent with myeloschisis.
Figure 26.57 First-trimester screening. Midsagittal imaging in two 13-week fetuses shows normal (A) and abnormal (B) posterior brain views.
Three main fluid spaces should be visible in posterior brain: brainstem (BS), fourth ventricle (4TH), and cisterna magna (CM). The abnormal fetus has an obliterated cisterna magna (arrow); therefore only two fluid spaces are visible. The brainstem-to-brainstem-to-occipital bone (BS-BSOB) ratio is also elevated (1.2), suspicious for open spina bifida. Subsequent imaging revealed myeloschisis at the L4–L5 level. OB, Occipital bone; TH, thalamus.
• Long-term morbidity includes paraparesis and/or paraplegia, bowel and bladder dysfunction/incontinence, orthopedic abnormalities, hydrocephalus requiring repeat ventriculoperitoneal shunting, developmental delay, and learning disabilities.62
• Recurrence risk is 3%–5%; periconceptional folic acid supplementation (4 mg/d) reduces risk of recurrence by 70%.62
ANTENATAL MANAGEMENT
• Amniocentesis with microarray or noninvasive prenatal testing (NIPT) should be considered for karyotype; amniotic fluid shows increased AFP and acetylcholinesterase.
• Fetal echocardiogram is recommended to assess cardiac structure and function.
• Fetoscopic or open fetal in utero treatment to halt CSF leakage and thereby decrease Chiari II malformation reduces need for ventriculoperitoneal shunt placement by 50% (40% versus 82%; RR = 0.48; 95% CI, 0.36–0.64; P < .001) and improves motor function (walking independently at 30 months 42% versus 21%; RR = 2.01; 95% CI, 1.16–3.48) but increases preterm delivery <37 weeks compared with conventional postnatal treatment (80% versus 15%; P < .001).69
• Fetal intervention for ONTD should be performed at highly specialized fetal surgery centers with a multidisciplinary approach using patient selection criteria established in the Management of Myelomeningocele Study (MOMS) trial (Box 26.4).63,65,66,75-77
• Maternal complications with fetal surgery include infection, hemorrhage, placental abruption, and pulmonary edema76,78; higher risk with open fetal surgery (20.9%; 95% CI, 15.2–7.1) than with fetoscopic surgery (6.2%; 95% CI, 4.9–7.5).78
• Serial ultrasound examinations to monitor fetal growth, amniotic fluid, and worsening fetal condition.
• Fetal nonstress and/or biophysical profile testing twice weekly beginning at 32–34 weeks.
• Prenatal neonatology and pediatric neurosurgery consultation to discuss postnatal management and prognosis.
• Delivery in tertiary care facility is recommended.
• Although prior studies had shown benefit to prelabor cesarean as opposed to vaginal delivery,77,79 a recent metaanalysis showed no difference in motor–anatomic level (mean difference −0.10; 95% CI, −0.58 to 0.38), and those delivered vaginally were less likely to have sac disruption (OR = 0.46; 95% CI, 0.23–0.90) or require a shunt (OR = 0.37; 95% CI, 0.14–0.95).80
• In addition to usual obstetric indications, cesarean should be performed for breech presentation or severe hydrocephalus.
• Use nonlatex gloves during delivery to prevent latex sensitization.
NEONATAL MANAGEMENT
• Protect open spinal lesion and/or cyst from infection and drying by wrapping with moist sterile bandages and keep neonate in sterile isolette pending surgery (Figs. 26.59 and 26.60).
• Use nonlatex gloves to prevent latex sensitization.
• Immediate pediatric neurosurgery consultation.
• Prophylactic antibiotics pending surgery.
• Postnatal surgical repair should be performed following delivery as soon as feasible (<48 hours).
Figure 26.58 Cranial findings. Axial view of fetal cranium with open neural tube defect shows frontal scalloping (lemon sign) (arrows) and effacement of the cistern magna (banana sign) (arrowheads).
INCLUSION CRITERIA
Maternal age ≥18 years old
Gestational age 19 0/7 to 25 6/7 weeks
Normal karyotype
Vertebral defect at S1 level or higher
Hindbrain herniation noted on prenatal ultrasound and MRI
EXCLUSION CRITERIA
Multiple fetal gestation
Additional fetal anomalies
Fetal kyphosis ≥30 degrees
Rh isoimmunization
Placenta previa
History of prior spontaneous singleton preterm delivery (<37 weeks)
History of incompetent cervix or cervix <20 mm on transvaginal ultrasound
Uterine anomaly
Insulin-dependent pregestational diabetes
Body mass index ≥35
Maternal HIV, hepatitis B, or hepatitis C infection
Other coexisting serious maternal comorbidities
Inadequate maternal psychosocial support or maternal psychosocial limitations
Unable to travel and follow up
Modified from Peranteau WH, et al. Prenatal surgery for myelomeningocele. Curr Opin Obstet Gynecol. 2016;28:111.
BOX 26.4 INCLUSION AND EXCLUSION CRITERIA
FOR FETAL IN UTERO REPAIR OF
MENINGOMYELOCELE
KEY POINTS
• Most open neural tube defects are associated with elevated maternal serum alpha fetoprotein, which should prompt careful sonographic evaluation.
• Most neural tube defects are located in the fetal lumbosacral region.
• Typical intracranial findings (Chiari malformation, cerebral ventriculomegaly, bifrontal retraction) are indirect sonographic markers of open neural tube defects; if seen, the spine should be carefully evaluated to rule out spinal dysraphism.
• Supplemental folic acid before conception reduces risk of recurrent open neural tube defects by 70%.
Craniosynostosis
DEFINITION
Craniosynostosis is a premature closure of single or multiple calvarial sutures, producing cranial deformation. Cloverleaf skull (kleeblattschädel) is a characteristic severe form of craniosynostosis.
INCIDENCE AND EPIDEMIOLOGY
• Incidence of craniosynostosis is approximately 1:2000 live births.81
ETIOLOGY AND PATHOGENESIS
• Craniosynostosis and cloverleaf skull are caused by faulty cranial embryogenesis with premature suture fusion that prevents further expansion of that portion of the skull, with subsequent redirection of brain and calvarial growth bulging into regions of least resistance.82
• Craniosynostosis is a heterogeneous group of >100 different syndromic conditions with half having a genetic basis; genetic syndromes are more likely if multiple sutures are affected.81
• Premature fusion of cranial sutures may be caused by a combination of factors83
• Poor fetal brain growth, limiting mechanical forces that maintain suture patency
• Compressive strain from extrinsic forces (malpresentation, uterine fibroids, oligohydramnios)
• Intrinsic factors controlling calvarial bone growth and integrity of the sutures, with gene mutations inhibiting normal control of osteogenic proliferation and boundary formation
• The most common single-gene disorders involve mutations of FGFR2, FGFR3, TWIST1, and EFNB1.84
• Risk factors for nonsyndromic craniosynostosis include breech presentation (OR = 6.42; 95% CI, 3.60–11.43; P < .0001), twin gestation (OR = 4.73; 95% CI, 2.56–8.73; P <
.0001), and oligohydramnios (OR = 5.06; 95% CI, 2.05– 12.52; P = .0004), suggesting intrauterine compressive factors may promote premature suture fusion.85
DIAGNOSTIC FEATURES
• Craniosynostosis produces an irregular or asymmetric cranial shape on axial view, depending on number and location of prematurely closed sutures and order of suture fusion (Fig. 26.61).81,86
• Coronal—brachycephaly (Fig. 26.62)
• Sagittal—dolichocephaly (Fig. 26.63)
• Metatopic—trigonocephaly (Fig. 26.64)
Figure 26.59 Neonatal appearance of myelomeningocele. Neonate with approximately 7-cm cystic mass at lumbosacral region of lower back, consistent with myelomeningocele.
Figure 26.60 Neonatal appearance of myeloschisis. Open, flatappearing lumbosacral neural tube defect approximately 4–5 cm long, consistent with myeloschisis.
• Unilateral coronal or lambdoidal—plagiocephaly (Fig.
26.65)
• Lambdoid plus coronal—acrocephaly (excessively elevated or conical cranium) (Fig. 26.66)
• Various complex combinations of coronal, lambdoidal, squamous, and sagittal sutures—cloverleaf skull (enlarged trilobed head) (Figs. 26.67 and 26.68; Video 26.34)
• Most common nonsyndromic craniosynostoses affect the sagittal (40%–55%), unilateral coronal (20%–25%), or metopic (5%–15%) sutures; 5%–15% involve more than one suture.86,87
• Echolucent fontanelle and cranial sutures may be visible on sagittal imaging around 16 weeks’ gestation.82
Figure 26.61 Patterns of skull deformation with premature fusion of cranial sutures in craniosynostosis. Premature cranial suture fusion causes redirection of calvarial growth into areas with less resistance (arrows).
Figure 26.62 Brachycephaly. Axial view at 17 weeks’ gestation shows unusually “rounded” calvaria with biparietal diameter (BPD) in the 94th percentile and cephalic index 86% (high), consistent with brachycephaly.
Figure 26.63 Dolichocephaly. Axial view at 23 weeks’ gestation shows biparietal diameter (BPD) in less than 2nd percentile. Cephalic index was 56% (low), consistent with dolichocephaly. Dolichocephaly is common in breech fetuses and should be reassessed.
Figure 26.64 Trigonocephaly. Axial view at 26 weeks’ gestation shows a flattened occiput (arrowheads) and pointed frontal calvaria, consistent with trigonocephaly.
• The cephalic index (biparietal diameter × 100/occipitofrontal diameter) may be helpful to distinguish normal shape of the fetal calvarium and should be 0.70–0.86. High cephalic index indicates brachycephaly; low cephalic index is dolichocephaly.
• Sensitivity for prenatal detection of isolated cranial deformities by ultrasound is poor and may not become apparent until the third trimester, but specificity to rule out craniosynostosis is excellent.
Figure 26.65 Plagiocephaly. Irregularly shaped calvaria, consistent with plagiocephaly, in this case caused by premature unilateral fusion of the coronal suture, with poorly developed frontotemporal skull (arrowheads).
Figure 26.66 Acrocephaly. Calvaria seen with elongated forehead. Imaging also revealed bilateral hydrocephalus and moderate proptosis in this fetus, and Pfeiffer syndrome was postnatally diagnosed.
Figure 26.67 Cloverleaf skull, axial. On axial view, complex combination of premature suture closure produces bulging temporal areas of the fetal calvaria (arrowheads) and a cloverleaf appearance.
PROFILE
Figure 26.68 Cloverleaf skull, sagittal. On sagittal view, occipital portion of calvaria bulges posteriorly (arrowheads) with cloverleaf skull. Thanatophoric dwarfism was diagnosed.
• Prenatal 3D and/or MRI to assess cranial sutures may be helpful to confirm diagnosis.88
DIFFERENTIAL DIAGNOSIS
• Other conditions that manifest with abnormally shaped calvaria on ultrasound
• Bifrontal retraction (“lemon”-shaped head) with spinal meningomyelocele
• Encephalocele
• Brachycephaly with trisomies 13, 21 (see Fig. 26.62) or “strawberry”-shaped head with trisomy 18 (Fig. 26.69)
• Intrauterine congenital deformation (prolonged rupture of membranes or breech position) producing positional plagiocephaly
• Calvarial deformation with pressure in skeletal dysplasia (Fig. 26.70)
• Obstructive hydrocephalus
ASSOCIATED ANOMALIES
• Careful ultrasound survey should be performed to rule out other associated abnormalities.
• Craniosynostosis is an isolated finding in 85% of cases.81,86
• Proptosis and hypotelorism or hypertelorism may result from shallow orbits and abnormal facial bone development.
• Syndromic craniosynostosis includes81,89
• Genetic diseases (Apert, Crouzon, Pfeiffer, Carpenter, Saethre-Chotzen syndromes)
• Skeletal dysplasias (cloverleaf skull with thanatophoric dysplasia)
• Disruptions (amniotic bands or limb–body wall complex)
• Malformations caused by teratogen exposure (valproic acid, hydantoin)
• Apert syndrome accounts for 40%–50% of syndromic craniosynostosis.86
• Approximately 40% of cases of classic cloverleaf skull are
due to thanatophoric dysplasia; 30% are due to monogenetic disorders; 20% are isolated cases; 10% are associated with other syndromes.89
PROGNOSIS
• Prognosis of craniosynostosis and cloverleaf skull depends on other associated abnormalities and whether the finding is part of a syndrome.
• Isolated brachycephaly and dolichocephaly typically have a normal outcome.
• Severe craniosynostosis (e.g., cloverleaf skull) is often associated with a lethal diagnosis (e.g., thanatophoric dwarfism).
• Syndromic craniosynostosis may be associated with mental retardation (Apert syndrome).
• Nonsyndromic craniosynostosis increases risk of neurodevelopmental delay and learning disabilities, with lower Bayley and Preschool Language Scale testing scores.90
• Ongoing craniofacial and/or neurosurgical treatment may be necessary.
• Early surgical treatment may reduce risk of brain compression with improved neurodevelopmental outcome, with most affected children in the United States undergoing cranial surgery within the first year of life.90
ANTENATAL MANAGEMENT
• Amniocentesis with microarray testing or noninvasive prenatal testing (NIPT) should be considered for gene mutation testing (e.g., FGFR2 or FGFR3 mutations) if there is a family history of inherited craniosynostosis.
Figure 26.69 Strawberry skull. Axial view at almost 16 weeks’ gestation shows a relative brachycephaly and pointed frontal bones, giving a “strawberry” appearance. The fetus was diagnosed with trisomy 18.
Figure 26.70 Skeletal dysplasia. Poorly mineralized calvarium at 26 weeks deforms with pressure from the ultrasound probe but returns to normal shape on releasing pressure.
• Cell-free fetal DNA (cffDNA) has been shown to detect FGFR2 and FGFR3 mutations using next-generation sequencing with 96% (95% CI, 81%–99.3%) sensitivity and 100% (95% CI, 85%–100%) specificity.91
• Serial ultrasound examinations to monitor fetal growth, amniotic fluid (polyhydramnios common), and cerebral ventricular size (ventriculomegaly common).
• Intrauterine fetal surgery has been proposed.
• Prenatal neonatology and genetics consultation to discuss postnatal management and prognosis.
• Consider prenatal consultation with pediatric neurosurgery and/or maxillofacial surgery.
• Delivery in tertiary care facility is recommended if a syndrome is suspected.
• Cesarean delivery may be warranted with macrocephaly.
NEONATAL MANAGEMENT
• Airway management may be an issue, necessitating tracheostomy with some forms of craniosynostosis.
• CT imaging with 3D reconstruction to confirm diagnosis.86
• Craniosynostosis is best managed at multispecialty tertiary care unit.
• Early intervention may prevent visual impairment, deafness, and cognitive defects.87
• Pediatric neurosurgery and/or maxillofacial surgery consultation as appropriate.
• Surgical management directed toward correcting skull deformity, preventing progression, and reducing risk of developing increased intracranial pressure.84
• Genetics consultation to help formulate diagnosis and prognosis.
• Positional plagiocephaly may necessitate orthotic helmets to mold the infant’s cranium to a normocephalic appearance.92
• Recurrence risk is 2%–10% with nonsyndromic craniosynostosis without molecular or cytogenetic diagnosis.84
KEY POINTS
• On axial view, the fetal calvaria should appear smoothly oval; an irregular or asymmetric cranial shape should prompt suspicion for craniosynostosis.
• Although most cases of craniosynostosis are isolated, careful anatomic survey should be performed to rule out other associated abnormalities and syndromes, particularly if there is cloverleaf skull or acrocephaly.
• Craniosynostosis should be treated via a multispecialty approach.
Hemivertebrae
DEFINITION
Hemivertebrae are triangular-shaped vertebrae in which only one-half of the vertebral body develops, causing scoliosis and/or kyphosis, which are abnormal angulations of the spine.
INCIDENCE AND EPIDEMIOLOGY
• Incidence of hemivertebrae is approximately 0.5–1:1000 live births, with male-to-female ratio of 1:3.93
ETIOLOGY AND PATHOGENESIS
• Hemivertebrae are defects of either vertebral body formation or segmentation during weeks 4–6 of gestation,94 owing to inadequate embryonic vascular supply to the lateral intersegmental portion of the developing chondral center.93
• Unilateral failure produces a wedge vertebra with asymmetric lateral vertebral height; complete failure results in a hemivertebra with a triangular-shaped vertebra that may be segmented (i.e., separated above and below by a disk space), partially segmented, or unsegmented (i.e., completely fused to the vertebrae above and below the hemivertebra).95
• Teratogens associated with congenital vertebral malformations include valproic acid, phenytoin, retinoic acid, alcohol, hyperthermia, zinc or folic acid deficiency, organophosphate pesticide exposure, and poorly controlled maternal diabetes.96
• Classification of hemivertebrae97
• Unsegmented—hemivertebra fused to vertebral bodies located superiorly and inferiorly in vertebral column
• Partially segmented—hemivertebra fused to the vertebral body above or below
• Fully segmented—hemivertebra separated from vertebral bodies above and below by a disk space
• Hemivertebrae act as a wedge against adjacent normal vertebral bodies,93 causing
• Scoliosis, an abnormal lateral curvature of the spine
• Kyphosis, an abnormal ventral curvature of the spine
• Lordosis, an abnormal dorsal curvature of the spine
• Shortening of the spine
DIAGNOSTIC FEATURES
• On ultrasound, abnormal curvature of the spine (Figs. 26.71 and 26.72; Video 26.35) should prompt a more thorough investigation with the spine visualized in sagittal, axial, and coronal planes.
• Segmentation anomalies appear as abrupt angulation or vertebrae appear out of parallel alignment (Figs. 26.73 and 26.74; Video 26.36).
• Hemivertebrae appear as a triangular structure, typically smaller than a full-sized vertebra, with an absent or diminutive contralateral vertebral element (Fig. 26.75).
• Approximately one-third have multiple nonadjacent hemivertebrae (Fig. 26.76).95
• Hemivertebrae are most commonly located in midthoracic and lower lumbar spine.98
• On first-trimester nuchal screening ultrasound, hemivertebrae should be suspected if an abrupt change in curvature of the spine is seen on sagittal or coronal views of the fetus.99
• 3D and/or MRI may be helpful to confirm diagnosis (Figs. 26.77 and 26.78).100
DIFFERENTIAL DIAGNOSIS
• Transient positional curvature of the spine
• Caudal regression
• Open neural tube defect (Fig. 26.79)
• Limb–body wall complex (Fig. 26.80)
• Amniotic band sequence
• Arthrogryposis
Figure 26.71 Mild scoliosis. Mildly rotated coronal view at 13 weeks shows mild angulation in upper lumbar region (arrow), suspicious for scoliosis. The spine should be further imaged for hemivertebrae.
Figure 26.72 Marked lordosis. Axial image shows more marked spinal lordotic curvature of the lumbar spine; skeletal dysplasia was diagnosed.
ASSOCIATED ANOMALIES
• Approximately two-thirds of fetuses with hemivertebrae have additional sonographic abnormalities.96,97,101
• Neural-axial abnormalities (tethered cord, Chiari malformation, intradural lipomas)
• Skeletal anomalies (spine, ribs, extremities)
• Nonskeletal anomalies (cardiovascular, genitourinary, CNS, gastrointestinal)98
• Hemivertebrae may be a component of a syndrome.93,101
• VACTERL association
• Jarcho-Levine
• Klippel-Feil
• Robinow
• Poor fetal growth in 20%–25%.98
Figure 26.73 Angulation defect. Coronal view of the spine at 21 weeks shows angulation at the thoracolumbar region, consistent with scoliosis.
Figure 26.74 Hemivertebra. Image shows a hemivertebra (arrow) with corresponding mild scoliosis. The posterior element opposite to the hemivertebra appears absent.
PROGNOSIS
• Prognosis of hemivertebrae and abnormal spinal curvature depends on other associated abnormalities (e.g., congenital heart defects, syndromes) and whether the hemivertebra is isolated or multiple segmental abnormalities are seen.
• Additional sonographic abnormalities with hemivertebrae increase risk of perinatal mortality (OR = 4.1; P = .042).101
Figure 26.75 Segmentation anomaly. Coronal view shows a segmentation anomaly of lumbar spine with a posterior element out of alignment with the remainder of the spine (arrow).
Figure 26.76 Multiple segmentation anomalies. Mildly rotated view of thoracolumbar junction shows multiple segmentation anomalies (arrows), consistent with hemivertebrae.
Figure 26.77 Hemivertebra, 3D imaging. 3D image of fetal spine shows a hemivertebra at thoracolumbar junction (arrow), causing mild scoliosis.
Figure 26.78 Marked scoliosis. 3D image shows segmental anomalies and marked scoliosis with hemivertebrae in the cervical and thoracic spine (arrows). Note the rib crowding in the area of the thoracic defect (arrowheads).
• Progressive curvature of the spine occurs rapidly during the first 5 years of life and again during the adolescent growth period in puberty, with anomalies at the cervicothoracic and lumbosacral junctions producing more visible deformities than other regions of the spine.97
• Early diagnosis and monitoring may improve outcome with early physical therapy and/or surgical intervention.
• Surgery may be required if there is marked progressive curvature, pain, or disfigurement; 75% exhibit significant worsening of spinal curvature.
• Serial derotational casting may be a temporizing treatment, which can allow delay in surgical intervention for approximately 2 years.
• Surgical treatment indicated if increasingly severe deformity or at high risk of progression (65%–85% of untreated patients develop curves in excess of 40 degrees after 10 years of age).96
• Surgical procedures include in situ hemivertebra fusion/ resection, vertical expandable prosthetic titanium rib (VEPTR) technique, and growing spinal rods to treat congenital spinal deformities.
• Long-term prognosis with isolated hemivertebra is excellent; most are detected as an incidental finding.
ANTENATAL MANAGEMENT
• Amniocentesis with microarray testing or noninvasive prenatal testing (NIPT) should be considered for karyotype and/or gene mutation studies if other associated anomalies are suspected.
• Fetal echocardiogram is recommended to assess cardiac structure and function, particularly if there is severe scoliosis or there are other associated abnormalities.
• Serial ultrasound examinations to monitor fetal growth and worsening fetal condition.
• Prenatal neonatology and pediatric orthopedic surgery consultation to discuss postnatal management and prognosis.
• Delivery in tertiary care facility is recommended only if there are other associated abnormalities or a syndrome is suspected.
• Cesarean delivery should be reserved for usual obstetric indications.
NEONATAL MANAGEMENT
• Usual neonatal care for most cases of isolated hemivertebra.
• Careful physical examination should be performed for other congenital anomalies and/or syndromes.
• Neonatal chest x-ray may reveal occult hemivertebrae (Fig. 26.81) and/or compressed ribs (Fig. 26.82).
• Postnatal pediatric orthopedic surgery consultation.
KEY POINTS
• Abnormal angulations of the fetal spine suggest hemivertebrae and scoliosis.
• Fetal 3D skeletal imaging is an excellent modality for assessing the fetal spine in detail.
• Most cases of significant scoliosis and other severe spinal angulations have other associated abnormalities and/ or are part of a syndrome with poor prognosis; however, cases of isolated hemivertebrae have an excellent longterm prognosis.
Amniotic Band Syndrome
DEFINITION
Amniotic band syndrome is a heterogeneous collection of atypical congenital malformations occurring in a nonembryonic distribution, possibly associated with early amnion rupture.
Figure 26.79 Open neural tube defect. Fetus at 21 weeks with lumbosacral neural tube defect (arrow) causing abrupt angulation defects.
Figure 26.80 Limb–body stalk anomaly. Fetus at 14 weeks with abdominoschisis, with abdominal contents adherent to posterior placenta (arrowheads) producing kyphoscoliotic angulations of the spine.
INCIDENCE AND EPIDEMIOLOGY
• Incidence of amniotic band syndrome is approximately 1:1200 to 1:15,000 live births; African Americans are affected 1.76 times more frequently than Whites.102
ETIOLOGY/PATHOGENESIS
• Three theories for amniotic band syndrome development102
• Intrinsic—deficient germline in embryonic development causes fetal malformations.
• Extrinsic—rupture of amniotic sac before amnion and chorion fusion causes the fetus to pass into chorionic cavity, and fragments of the ruptured amnion form fibrous constriction bands surrounding fetal parts, which gradually lead to lymphedema, vascular insufficiency, and necrosis.
• Vascular—disrupted blood supply to developing embryo (e.g., emboli from chorionic villus sampling) causes necrosis and deformation.
• Clinical manifestations of amniotic band syndrome102
• Disruption—breakdown of normal tissue from any cause (e.g., constriction bands with amputations)
• Deformation—abnormal forces on normal tissue (e.g., clubfoot, joint contractures with oligohydramnios)
• Malformation—early insult results and abnormal development of an organ (e.g., body wall and craniofacial abnormalities)
DIAGNOSTIC FEATURES
• Fetal deformities seen in random, asymmetric, and nonembryonic distribution (Figs. 26.83–26.85; Video 26.37) with or without associated amniotic bands visualized; however, if amnion is seen adherent to affected fetal parts, this is pathognomonic for amniotic band syndrome (Fig. 26.86; Video 26.38).102,103
• Specific fetal malformations depend on gestational age of ruptured membranes and location of fetal part attached to fibrous membrane band.104
Portable
Figure 26.81 Neonatal thoracolumbar hemivertebra. Anteriorposterior radiograph in neonate clearly shows hemivertebra (arrow) at thoracolumbar region of the spine, causing scoliosis.
Figure 26.82 Neonatal thoracic hemivertebra. Anterior-posterior radiograph in neonate demonstrates hemivertebra (arrow) in the thoracic vertebrae, with corresponding scoliosis and rib crowding (arrowheads).
Figure 26.83 Missing fingers. Upper extremity shows intact thumb (arrowhead), but the digits are either absent or foreshortened (arrows), consistent with amniotic band syndrome.
• First-trimester disruption produces craniofacial and visceral defects (Video 26.39).
• Second- or third-trimester disruption causes constriction rings, lymphedema, and limb amputation.
• Most common abnormalities are limb or digit amputation, constriction rings, and acrosyndactyly (distal syndactyly of digits).102
• Affected fetal parts (excluding limb–body stalk complex, discussed in Chapter 24)103
• Hands and/or feet (90%)
• Umbilical cord (30%)
• Abdomen (20%)
• Head (5%)
• Chest (5%)
• High-frequency transducer may be necessary to reveal amniotic band(s) or sheet(s) (Video 26.40).
• Severity of isolated extremity involvement in amniotic band syndrome is classified in Table 26.4.
• Color Doppler ultrasound and MRI may be helpful adjuncts.
DIFFERENTIAL DIAGNOSIS
• Limb–body stalk anomaly (short umbilical cord, lacks limb defects)
• Multiple pterygium
• Amniotic sheets without fetal involvement (Video 26.41)
• Uterine synechiae or septations (Fig. 26.87)
• Amnion-chorion separation
• Empty gestational sac from lost twin
• Circumvallate placenta
• Teratogen exposure affecting limb morphogenesis (thalidomide, warfarin, phenytoin, valproic acid, cocaine, misoprostol), usually bilateral and symmetric102
• Genetic syndromes with embryonic failure of transverse distal extremity formation (rudimentary short fingers and fingernails)102
Figure 26.84 Missing hand. Image shows most of the hand is absent beyond the metatarsals (arrows). No amniotic membranes were apparent on imaging or following delivery.
Figure 26.85 Missing toes. Image shows missing middle toes (arrow). This appearance is similar to ectrodactyly but was confirmed as amniotic band syndrome at delivery.
Figure 26.86 Amniotic bands. Image shows fetal hand (arrow) entangled within amniotic membranes (arrowheads). At delivery, three distal fingertips were absent.
• Symbrachydactyly
• Adams-Oliver syndrome
• Ectrodactyly-ectodermal dysplasia (EED)
• See Fig. 24.23 for diagnostic algorithm for diagnosing suspected fetal abdominal wall defects.
ASSOCIATED ANOMALIES
• Craniofacial abnormality (atypical cleft lip/palate, nasal deformity, ophthalmic defects)
• Neural tube defects (asymmetric encephalocele, anencephaly)
• Body wall defect (“slash defects”)
• Clubfoot
• Scoliosis
• Preterm delivery in 35%–50%
• May be associated with vaginal bleeding and/or premature rupture of the membranes (PROM)102
PROGNOSIS
• Long-term prognosis depends on body areas affected.
• Severe craniofacial deformities are likely lethal.
• Visceral defects depend on extent of abnormality and surgical correction.
• Umbilical cord involvement (Fig. 26.88) more likely to result in perinatal loss (67% versus 19%; P = .05).103
• Limb defects are typically associated with normal life expectancy with varying degrees of disability.
ANTENATAL MANAGEMENT
• Consider termination if lethal or uncorrectable anomalies are present.
• Consider amniocentesis with microarray testing or noninvasive prenatal testing (NIPT) if uncertain diagnosis.
• Serial ultrasound examinations to monitor fetal growth, amniotic fluid, and worsening fetal condition (e.g., hydrops fetalis).
• Doppler imaging of fetal extremities with suspected constriction bands should be performed weekly to evaluate vascular flow proximal and distal to constriction site and compared with the contralateral extremity; normal vascular flow makes fetal intervention unnecessary.105
• Fetoscopic in utero release of amniotic bands has been proposed,105-108 with an overall 75% reported success rate in
Figure 26.87 Uterine synechiae. Thick band of tissue extending anterior to posterior within the uterus (arrowheads) with fetal parts seen on both sides, consistent with uterine synechiae.
Prenatal Classification of Amniotic Band
Syndrome Involving Fetal Extremities
Stage I Amniotic bands without signs of constriction
Stage II Constriction without vascular compromise (normal
Doppler studies, compared to contralateral
extremity); may have distal deformity
II-A: Absent or mild lymphedema
II-B: Severe lymphedema
Stage III Severe constriction with progressive arterial
compromise (Doppler flow measured at, proximal
to, and distal to the constriction band)
III-A: Abnormal distal Doppler studies compared to
contralateral extremity
III-B: Absent vascular flow to extremity
Stage IV Bowing or fracture of long bones at constriction site
Stage V Intrauterine amputation
Figure 26.88 Amniotic band and umbilical cord. Pathology photograph of placenta and umbilical cord following intrauterine fetal demise. A band of amniotic fluid is tightly bound around the umbilical cord (arrowhead).
preserving limb function, but complicated by preterm PROM (less than 37 weeks) in 50% and preterm delivery in 64%.108
• Photocoagulation using neodymium/yttriumaluminum-garnet (Nd:YAG) laser
• Fulgurating diathermy electrode
• Laparoscopic hook cautery
• Mechanical lysis with endoscopic scissors/graspers
• Fetal nonstress and/or biophysical profile testing twice weekly beginning at 32–34 weeks.
• Prenatal neonatology, pediatric orthopedics, pediatric surgery, and genetics consultation to discuss postnatal management and prognosis.
• Delivery in tertiary care facility is recommended if nonextremity defects are present.
• Unmonitored labor is appropriate if lethal anomalies (e.g., severe craniofacial anomalies) are present.
• Cesarean delivery should be reserved for usual obstetric indications.
• Placenta and membranes for pathology review.
NEONATAL MANAGEMENT
• Careful examination of neonate is important to assess for congenital anomalies not previously detected on ultrasound (Fig. 26.89).
• Surgical repair likely warranted, depending on final postnatal findings and diagnosis.
• Pediatric surgery and orthopedic surgery consultations as appropriate.
KEY POINTS
• Amniotic band syndrome describes the atypical nonembryonic (isolated) pattern of fetal malformation, which may or may not involve amniotic bands, per se.
• Tissue disruption early in gestation causes more extensive craniofacial/visceral defects, whereas later disruption mainly involves distal extremities.
• Preterm delivery is common with amniotic band syndrome.
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