Split hand‐foot malformation, tetralogy of Fallot, mental retardation and a 1 Mb 19p deletion—evidence for further heterogeneity?

• Published in: American journal of medical genetics. Part A Vol. 149A; no. 5; pp. 975 - 981
• Main Authors: Aten, Emmelien, den Hollander, Nicolette, Ruivenkamp, Claudia, Knijnenburg, Jeroen, van Bokhoven, Hans, den Dunnen, Johan, Breuning, Martijn
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2009; Wiley-Liss
• Subjects: 19p deletion; Adult and adolescent clinical studies; Angelman Syndrome - genetics; Biological and medical sciences; Chromosome Deletion; Chromosomes, Human, Pair 19 - genetics; Foot Deformities, Congenital - genetics; Genetic Heterogeneity; Hand Deformities, Congenital - genetics; Humans; Intellectual deficiency; Intellectual Disability - genetics; Male; Medical genetics; Medical sciences; mental retardation; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; split hand foot malformation; Syndrome; tetralogy of Fallot; Tetralogy of Fallot - genetics; Chromosomal aberration; Diseases of the osteoarticular system; Split-hand split-foot syndrome; Developmental disorder; tetralogy of Fallot; Mental retardation; Genetic disease; Heterogeneity; 19p deletion; split hand foot malformation; Disease of the hand; Malformation; Disease of the foot; Intellectual deficiency; Deletion
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32748

Congenital limb malformations are the second most common birth defects observed in infants. Split hand foot malformation (SHFM), also known as central ray deficiency, ectrodactyly and cleft hand/foot, occurs isolated or in combination with other malformations. We report on a male patient with SHFM, tetralogy of Fallot and a clinical phenotype suggestive of Angelman syndrome. Using array based genome analysis (3K BACs and 500K SNPs), we identified a de novo deletion of chromosome 19p13.11, confirmed by Fluorescent In Situ Hybridization analysis. The deletion is 0.99 Mb in size and contains 28 genes. The proximal breakpoint of the deletion is in EPS15L1, which may be involved in vertebrate limb development. Subsequent screening of 21 syndromic and nonsyndromic SHFM patients (TP73L mutation negative) for rearrangements using Multiplex Ligation‐dependent Probe Amplification did not detect other deletions or duplications in chromosome 19. These findings suggest that our patient may have a new contiguous gene syndrome and indicates that SHFM is genetically more heterogeneous than currently known. © 2009 Wiley‐Liss, Inc.