Partial Monosomy of Chromosome 5 in 2 Male Siblings – Phenotypic Correlates

Abstract

We describe the phenotypes of two male siblings with partial monosomy of chromosome 5 [46XY,del(5q34q35.3)]; maternally derived from a balanced insertion of 1 and 5 [inv. ins (1:5) (p.32; q35.3:3q34)]. Sib #1, (8 yrs.) - microcephaly, cleft lip and palate, facial dysmorphism, atrial (ASD) and ventricular (VSD) septal defects, contractions of fingers, tight hamstrings, developmental delay. Sib #2, (2 months) - small stature, ASD, hypotonia, primary optic nerve hypoplasia. Only 4 patients with distal 5 q deletions have been reported and none showed the putative breakpoints identified in our 2 patients. All 6 showed developmental delay; 4 of 6 had defects of cardiac septation. Our 2 patients and 1 other were shown to have only one copy of the cardiac specific hCSX gene which defines in part the etiology of their ASD and VSD. Isolated mutations of the hCSX gene encoding homeobox transcription factor NKX2-5 have been shown to produce nonsyndromic septation defects (ASD) in 4 families. Deleted contiguous genes may account for other phenotypic features in our patients.