A prenatal case of split-hand malformation associated with 17p13.3 triplication – A dilemma in genetic counseling

• Published in: European journal of medical genetics Vol. 57; no. 2; pp. 81 - 84
• Main Authors: Luk, H.M, Wong, Vincent C.H, Lo, Ivan F.M, Chan, Kelvin Y.K, Lau, Elizabeth T, Kan, Anita S.Y, Tang, Mary H.Y, Tang, W.F, She, Wandy M.K, Chu, Yoyo W.Y, Sin, W.K, Chung, Brian H.Y
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Masson SAS 01.02.2014
• Subjects: 17p13.3 copy number gain; Adult; Autism; Autopsy; Chromosomes, Human, Pair 17; Comparative Genomic Hybridization; Developmental delay; DNA Copy Number Variations; Female; Genetic Counseling; Hand Deformities, Congenital - diagnosis; Hand Deformities, Congenital - genetics; Humans; Medical Education; Phenotype; Pregnancy; Prenatal diagnosis; Split hand malformation; Trisomy; Ultrasonography, Prenatal; Autism; Prenatal diagnosis; 17p13.3 copy number gain; Developmental delay; Split hand malformation
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2013.12.005

Abstract Copy number gain of 17p13.3 has been shown to be associated with developmental delay/autism and Split-Hand-Foot malformation. We report a case of fetus with bilateral split-hand malformation detected on prenatal ultrasound. Array comparative genomic hybridization detected 2 maternally inherited copy number gains in the 17p13.3 region with one of them involving the BHLHA9 gene and part of the YWHAE gene. The mother is normal in intelligence with mild right foot anomaly only. Although the BHLHA9 copy gain is known to be associated with split-hand-foot malformation, the penetrance and expressivity is highly variable. More challenging is the effect of partial YWHAE copy number gain on neurodevelopment is inconclusive based on current literature. This case highlights the difficulties of prenatal genetic counseling in array comparative genomic hybridization findings in clinical situation with incomplete understanding of genotype–phenotype correlation.