title: A prenatal case of split-hand malformation associated with 17p13.3 triplication - a dilemma in genetic counseling.
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.
authors.affiliation: Clinical Genetic Service, Department of Health, Hong Kong, China.
authors.forename: H M
authors.initials: HM
authors.lastname: Luk
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Vincent C H
authors.initials: VC
authors.lastname: Wong
authors.affiliation: Clinical Genetic Service, Department of Health, Hong Kong, China.
authors.forename: Ivan F M
authors.initials: IF
authors.lastname: Lo
authors.affiliation: Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Prenatal Diagnostic and Counseling Department, Tsan Yuk Hospital, Hong Kong, China.
authors.forename: Kelvin Y K
authors.initials: KY
authors.lastname: Chan
authors.affiliation: Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Prenatal Diagnostic and Counseling Department, Tsan Yuk Hospital, Hong Kong, China.
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Lau
authors.affiliation: Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Department of Obstetrics & Gynaecology, Queen Mary Hospital, Hong Kong, China.
authors.forename: Anita S Y
authors.initials: AS
authors.lastname: Kan
authors.affiliation: Prenatal Diagnostic and Counseling Department, Tsan Yuk Hospital, Hong Kong, China.
authors.forename: Mary H Y
authors.initials: MH
authors.lastname: Tang
authors.affiliation: Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: W F
authors.initials: WF
authors.lastname: Tang
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Wandy M K
authors.initials: WM
authors.lastname: She
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Yoyo W Y
authors.initials: YW
authors.lastname: Chu
authors.affiliation: Department of Obstetrics & Gynaecology, Tuen Mun Hospital, Hong Kong, China.
authors.forename: W K
authors.initials: WK
authors.lastname: Sin
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Electronic address: bhychung@hku.hk.
authors.forename: Brian H Y
authors.initials: BH
authors.lastname: Chung
mesh_terms: D000328:Adult; D001344:Autopsy; D002886:Chromosomes, Human, Pair 17; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D005817:Genetic Counseling; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D011247:Pregnancy; D014314:Trisomy; D016216:Ultrasonography, Prenatal
keywords: 17p13.3 copy number gain; Autism; Developmental delay; Prenatal diagnosis; Split hand malformation