Hemifacial Microsomia with Spinal and Rib Anomalies: Prenatal Diagnosis and Postmortem Confirmation Using 3-D Computed Tomography Reconstruction

Abstract

Hemifacial microsomia (OMIM164210) is a condition featuring unilateral ear anomalies and ocular epibulbar dermoids associated with unilateral underdevelopment of the craniofacial bony structures. Other associated anomalies have also been described, especially spinal malformations, and the term oculoauriculovertebral dysplasia spectrum (OVAS) was suggested to include the three predominant systems involved. Both genetic and environmental causes are implied in the pathogenesis of the syndrome, with a 3% recurrence rate according to reports of both vertical transmission and affected siblings. No specific gene was identified, albeit mutations in chromosome 10 and deficiencies of genes in the endothelin pathway in mice exhibited the same clinical features. We hereby describe the first case of prenatal diagnosis of spinal and rib malformations associated to hemifacial microsomia by means of 2-D and 3-D ultrasound in a 23-week fetus. The sonographic study depicted fetal scoliosis due to the presence of hemivertebrae, Sprengel’s deformity of the left shoulder, ribs fusion, asymmetric ears with unilateral microtia, mandible unilateral hypoplasia as well as single umbilical artery and a ‘golf ball’ sign in the left ventricle of the heart. The diagnosis of OVAS was suggested and the family received proper genetic consultation. After termination of the pregnancy, the syndrome was confirmed by postmortem 3-D computed tomography study. In view of the grim outcome, prenatal death rate and high mortality and morbidity when three or more systems are involved, prenatal diagnosis and appropriate counseling are warranted.

Genetics of non‐isolated hemivertebra: A systematic review of fetal, neonatal, and infant cases

“…We identified 59 cases of non‐isolated hemivertebra attributed to single gene disorders with a known molecular etiology as confirmed in OMIM and/or HPO query (Table 3): Jarcho‐Levin syndrome and other spondylocostal dysostoses ( DLL3, MESP2, LFNG, HES7, TBX6, RIPPLY2 ), 38–55 Craniofacial microsomia ( SF3B2, MYT1 ), 56–62 Robinow syndrome ( ROR2, WNT5A, DVL1, DVL3 ), 63–65 Klippel‐Feil syndrome ( GDF6 ), 66,67 Alagille syndrome ( JAG1, NOTCH2 ), 68,69 caudal regression syndrome with peno‐scrotal transposition ( VANGL1 ), 70,71 caudal duplication syndrome ( AXIN1 ), 72 congenital disorders of glycosylation ( SLC35A3, ALG12 ), 73,74 CHARGE syndrome ( CHD7, SEMA3E ), 75 TARP syndrome ( RBM10 ), 76 chondrodysplasia punctata ( EBP ), 77 ectodermal dysplasia, ectrodactyly and cleft lip/palate syndrome ( TP63 ), 78 unilateral abdominal wall hypoplasia ( CHRM3 ), 79 BRESEK/BRESHECK syndrome ( MBTPS2 ), 80 renal cysts and diabetes syndrome ( HNF1β ), 81 congenital short bowel syndrome ( CLMP ), 82 and EVEN‐PLUS syndrome ( HSPA9 ) 83 . These syndromes currently have a known molecular basis that was not always reported at the time of publication of the specified cases.…”

“…Twenty of these HPO genes were identified in our search (Tables 1, 3, and S3). 22,38–65,68,75,77,80,93,97–99 The remaining 29 of 49 identified HPO genes associated with hemivertebra were not identified in our systematic review and are described in Table S4. Eight genes did not meet our age inclusion criteria and 12 were excluded as age was not specified in potential cases.…”

“…[56][57][58][59][60][61][62] Robinow T A B L E 2 Copy number variant changes associated with non-isolated hemivertebra diagnosed in the fetal, neonatal, and infant period Abbreviations: FISH, fluorescent in situ hybridization; L, lumbar vertebra; NR, not reported; TOP, termination of pregnancy.T A B L E 3 Syndromes associated with non-isolated hemivertebra diagnosed in the fetal, neonatal, and infant period with known single gene etiology Abbreviations: ACC, agenesis of the corpus callosum; ARSA, aberrant right subclavian artery; ASD, atrial septal defect; C, cervical vertebra; CDG, congenital disorder of glycosylation; CMA, chromosomal microarray; CNS, central nervous system; DOL, day of life; FGR, fetal growth restriction; IQ, intelligence quotient; L, lumbar vertebra; NR, not reported; PFO, patent foramen ovale; SNP, single nucleotide polymorphism; SUA, single umbilical artery; T, thoracic vertebra; TOP, termination of pregnancy; VSD, ventricular septal defect.a Low set ears, low…”

Minor Anomalies: Can They Predict Specific Major Defects? A Study Based on 23 Major and 14 Minor Anomalies in Over 25,000 Newborns with Birth Defects

“…However, overlapping of certain anomalies exists between VATER and the oculo auriculo vertebral (OAV) association, where microtia is a cardinal feature, 15 and at least one case with OAV and SUA has been described. 16 The greater frequency of ambiguous genitalia among cases with anal atresia þ SUA and microtia þ SUA was mainly due to an associated sirenomelia or a persistent cloaca. While anal atresia is a component of both anomalies, microtia is not, reinforcing the suspicion that the relationship between microtia and SUA depends on the presence of other defects, such as those found in the OAV association.…”

Prenatal and Neonatal Ultrasound and Magnetic Resonance Imaging Diagnosis of Sprengel’s Deformity with Unusual Associations

“…An initial diagnosis can often be made using radiography, but a CT or magnetic resonance imaging (MRI) is often necessary to evaluate the details of the abnormality. Using the keywords "Sprengel's deformity, prenatal diagnosis," we found only four publications in the PubMed database, one of which is not strictly related as it reports a case of a 6-year-old boy and only stresses that prenatal diagnosis is important [6]; therefore, the number of cases reported to date is three [7][8][9]. The authors present a case of prenatal ultrasound (US) diagnosis of Sprengel's deformity with further elucidation after birth and discuss unusual associations with this malformation as well as details that should have been recognized in prenatal MRI.…”