BackgroundDyssegmental dysplasia Silverman‐Handmaker (DDSH; MIM 224410) type is an extremely rare skeletal dysplasia caused by functional null mutations in the perlecan gene. Less than forty cases are reported in the literature, of which only four were prenatally detected.MethodsWe report on a dizygotic twin pregnancy from consanguineous parents for which one of the twins presented prenatally with severe micromelia, limb bowing and scoliosis, and postnatally with clinical and radiological features compatible with a diagnosis of dyssegmental dysplasia. Molecular studies were undertaken to confirm the clinical diagnosis of DDSH.ResultsMolecular analysis results revealed a novel homozygous variant in the HSPG2 gene (MIM 142461), NM_005529.6(HSPG2):c.4029 + 1G>A, consistent with a diagnosis of DDSH.ConclusionTo the best of our knowledge, the current report is only the seventh molecularly confirmed case of DDSH.
Key Clinical Message
Multiple genetic disorders can coexist in one patient. When the phenotype is not fully explained with one diagnosis, it is recommended to perform further genetic investigations in search for coexisting second diagnosis.
Abstract
Craniofrontonasal dysplasia (CFND) (MIM: 304110) is an X‐linked dominant disorder that shows paradoxically greater severity in heterozygous females than in hemizygous males. It is caused by a pathogenic variant in
EFNB1
. Pontocerebellar hypoplasia type 1B (PCH1B) (MIM: 614678) is an extremely rare condition with over 100 individuals reported to date. It is caused by biallelic pathogenic variants in
EXOSC3
. This report presents the case of a girl who was diagnosed prenatally with CFND based on the findings on the prenatal imaging and the known diagnosis of CFND in her mother. She has severe global development delay that cannot be explained solely by the CFND diagnosis. Around the age of 2 years, she was diagnosed with PCH1B following whole exome sequencing (WES) testing. The objective of this study is to highlight the importance of pursuing genetic investigation if the available genetic diagnosis cannot fully explain the clinical picture. This is a case report of one patient and review of the literature. Informed consent was obtained from the parents. WES was performed by a private lab using next‐generation sequencing (NGS), DNA was sequenced on the NovaSeq 6000 using 2 × 150 bp paired‐end read. WES identified the following: homozygous pathogenic variant in
EXOSC3
: C.395A>C, p.ASp132Ala, maternally inherited, likely pathogenic duplication at Xq13.1 (includes
EFNB1
) and paternally inherited 16p11.2 duplication that is classified as a variant of uncertain significance. Perusing more extensive genetic testing like: WES is indicated if the current genetic diagnosis cannot fully explain the phenotype in a patient.
Electronic poster abstracts shifted up from 3 rd centile at 29 weeks to 15 th centile at 35 weeks. Caesarean section was performed at 37 weeks presenting two female newborns weighting 2235 g on fetus A and 2680 on fetus B. We believe that some benefit with nutritional intervention may improve fetal outcome of twin fetus with selective IUGR. EP07.12 Dyssegmental dysplasia: clinical, radiological and molecular findings of a challenging antenatal diagnosis in a dizygotic twin pregnancy
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