17p13.3 class I microduplication in a newborn with microcephaly, aortic stenosis and dysmorphic facial features

Abstract

BACKGROUND: Deletion of chromosome 17p13.3 is known to result in Miller-Dieker Syndrome. Microduplication of the same genomic region results in a distinctive clinical syndrome (Roos et al. 2009). We report a newborn presented with dysmorphic features, microcephaly and congenital heart disease, who was confirmed to have 17p13.3 microduplication syndrome by array comparative genomic hybridization (aCGH). CLINICAL INFORMATION: The proband was the 2nd child of a non-consanguineous Chinese couple. He was noted to be microcephalic from fetal USG in China. He was born full term via LSCS with normal Apgar scores. His head circumference, body weight and height at birth were 31.5 cm (<3rd percentile), 3.33 kg (25-50th percentile) and 48 cm (10th percentile) respectively. Distinct facial features including flat midface, posteriorly rotated and low-set ears, fleshy earlobes and triangular chin. Echocardiogram revealed valvar aortic stenosis and tiny patent ductus arteriosus. USG brain was normal. Karyotype and FISH for Elastin gene were normal. aCGH by NimbleGen CGX-12 array identified a 790 kb copy number gain in the 17p13.3 region involving the YWHAE gene, but not the PAFAH1B1 gene. Bruno et al (2010) proposed that there are 2 classes of 17p13.3 microduplication. Class I involves YWHAE gene, but not PAFAH1B1 gene while Class II involves PAFAH1B1 gene, with or without CRK and YWHAE genes. Class I 17p13.3 microduplication is associated with autistic features, developmental delay and subtle dysmorphic features such as pointed chin, fleshy ears and cupid bow. Microcephaly has been reported but often there is a tendency to post-natal overgrowth. Only one patient in Bruno's cohort was noted to have cardiovascular manifestations, namely aortic root dilatation and mitral valve prolapse. CONCLUSION: To our knowledge, this is the first patient with 17p13.3 microduplication syndrome reported in Chinese. Growth and neuro-development need to be closely monitored. The young age of diagnosis together with the associated tendency to autism spectrum disorder pose a challenge in genetic counseling.