Distal 13q Deletion Syndrome and the VACTERL Association: Case report, literature review, and possible implications

Abstract

We present a case of a child with del(13) (q31.1qter), VACTERL association, and penoscrotal transposition. Deletion of the distal long arm of chromosome 13 is associated with variable phenotypes. These phenotypes are divided into three clusters; each cluster represents a specific deleted segment of 13q. Individuals with deletions of a critical region at 13q32 have multiple congenital malformations that include components of the VACTERL association. Our patient had all six manifestations of VACTERL association. In addition, he had complete penoscrotal transposition, a unique malformation reported rarely in VACTERL association and only twice previously in deletion of distal 13q. We reviewed all reported cases of distal 13q deletions to date. Of these 137 patients, 15 could be classified into the VACTERL association. Ours was the only patient with distal 13q deletion and all VACTERL association features and also the only one with tracheoesophageal fistula. Neither holoprosencephaly nor the other central nervous system malformations that have been seen in individuals with distal 13q deletions were apparent in him. The patient presented here appears to be unique among individuals with distal 13q deletion. His cluster of malformations strengthens the argument that distal 13q deletion is a cause for VACTERL association, and that this causal relationship implies a syndromic form of VACTERL. In addition, this case and those ascertained from the literature suggest that penoscrotal transposition should be considered part of both the distal 13q-deletion syndrome and some forms of VACTERL association.

De novo microduplications at 1q41, 2q37.3, and 8q24.3 in patients with VATER/VACTERL association

“…In accordance with this, previous studies have identified several de novo chromosomal microaberrations, which are likely to be disease causing. [5][6][7][8][9][10][11][12][13][14][15][16] However, none of these de novo chromosomal microaberrations has led to the identification of a disease-causing gene and the etiology in most cases is still unknown.…”

Familial occurrence of the VATER/VACTERL association

“…Reported environmental factors include maternal diabetes, uterine vascular pathology, and infertility treatment [13][14][15][16]. However, reports of familial occurrence [11], and the presence of chromosomal (micro-) aberrations in affected individuals [17][18][19][20][21][22][23][24] emphasize the importance of possible genetic factors in the etiology of the disorder.…”

Phenotypic expansion of the supernumerary derivative (22) chromosome syndrome: VACTERL and Hirschsprung's disease

“…This case highlights the phenotypic overlap of Emanuel syndrome and VACTERL association. Combinations of VACTERL defects have been reported in patients with trisomy 18, the 13q deletion syndrome, 4p deletion syndrome, an interstitial deletion of the long arm of chromosome 6, 9qh+, and mosaicism for a small supernumerary ring chromosome derived from the pericentromeric region of chromosome 12 [4,[9][10][11][12][13][14][15]. In addition, a germline mutation of the PTEN gene (chromosome 10q22-23) has been reported in one patient with VACTERL features [16].…”

“…Affecting 1 in 5000 live births, it is considered sporadic and multifactorial with no inheritance pattern identified so far [3]. Several etiologic factors have been proposed, including cytogenetic abnormalities, diabetes, Fanconi anemia, CCG repeat expansion in the fragile X syndrome, and mitochondrial disorders [4,5].…”