Whole exome sequencing, clinical exome or targeted gene panels: what to choose for suspected lethal skeletal dysplasia (short rib thoracic dysplasia type IV)

Lethal skeletal dysplasias (SDs) are a heterogeneous group of rare but important genetic disorders characterised by abnormal growth and development of bone and cartilage. The phenotypic variation of SD highlights the complex aetiology for this group of disorders. Short rib polydactyly syndrome (SRPS) types I-IV are a group of rare congenital autosomal recessive types of SD.We report a case of a non-consanguineous couple whose two successive pregnancies were diagnosed with multiple congenital anomalies in fetuses suggestive of lethal SD (likely SRPS type IV) at 24 and 19 weeks period of gestation, respectively. Pregnancy was terminated, and the whole exome sequencing of the abortus for genetic analysis in the second pregnancy confirmed an autosomal recessive type of short rib thoracic dysplasia-4 (SRTD-4) also called SRPS in homozygous condition. Our case is unique as it was also associated with cystic hygroma which is a rare association with SRPS/SRTD-4.