16p subtelomeric duplication: a clinically recognizable syndrome

Abstract

We report on two patients with duplication of the subterminal region of chromosome 16p (dup16p) recognized by fluorescent in situ hybridization (FISH) telomere analysis, presenting with closely overlapping facial features and neurological impairment. Distinct facial anomalies included high forehead, sparse eyebrows, blepharophimosis, short nose, everted upper lip, high-arched palate, wide-spaced teeth, and cupped anteverted ears. Susceptibility to vascular anomalies, in particular pulmonary hypertension and portal cavernoma, was found in one patient. Subtelomeric analysis by FISH demonstrated a de novo duplication of the subtelomeric region of chromosome 16p and a deletion of the subtelomeric region of chromosome 4q in case 1, and duplication of the subtelomeric region of 16p and a deletion of the subtelomeric region of 21q, resulting from malsegregation of a balanced maternal traslocation t(16pter;21qter) in case 2. The extension of duplicated regions measured by array-comparative genome hybridization was about 12 Mb on 16p13.3p13.13 in case 1, and about 8.5 Mb on 16p13.3p13.2 in case 2. In conclusion, we reported a clinically recognizable disorder in two patients with dup16p. Pulmonary hypertension, vascular ring, and manifestations of vascular disruption, as terminal hypoplasia of hands and aplasia cutis, have been previously described in association with dup16p. Thus, susceptibility to pulmonary vascular disease and other vascular anomalies can be a feature of dup16p, suggesting that this subtelomeric region in some respect could be related to vascular anomalies.

Intellectual disability secondary to a 16p13 duplication in a 1;16 translocation. Extended phenotype in a four‐generation family

“…Many of these subtelomeric deletions or duplications are now recognized as clinically recognizable phenotypes [Holinski-Feder et al, 2000;Battaglia et al, 2008;Digilio et al, 2009]. Partial trisomy 16p is however a rare chromosomal abnormality characterized by ID and multiple congenital abnormalities (MCA) [Leonard et al, 1992;Schinzel et al, 1997;Tschernigg et al, 2002;Sommer et al, 2006;Digilio et al, 2009]. Some authors had reported that a duplicated segment within 16p13 is responsible for the clinical manifestations of this disorder and likely the critical region [Schinzel et al, 1997;Tschernigg et al, 2002;Sommer et al, 2006;Digilio et al, 2009].…”

“…Duplication of 16p13.3 (RubinsteinTaybi syndrome region) also can cause a recognizable syndrome with mild to moderate ID, dysmorphic features, hand and foot anomalies as well as congenital heart defects in some cases [Marangi et al, 2008;Digilio et al, 2009;Thienpont et al, 2010;Chen et al, 2012].…”

“…It has been recognized that subtle rearrangements at the telomere regions may cause unexplained ID [Flint and Knight, 2003]. Many of these subtelomeric deletions or duplications are now recognized as clinically recognizable phenotypes [Holinski-Feder et al, 2000;Battaglia et al, 2008;Digilio et al, 2009]. Partial trisomy 16p is however a rare chromosomal abnormality characterized by ID and multiple congenital abnormalities (MCA) [Leonard et al, 1992;Schinzel et al, 1997;Tschernigg et al, 2002;Sommer et al, 2006;Digilio et al, 2009].…”

“…Furthermore, duplications of 16p13.3 may be terminal [Digilio et al, 2009] or interstitial [Nruzinia et al, 2009;Thienpont et al, 2010;Chen et al, 2012]. In addition, these duplications can be inherited from parental balanced reciprocal translocations [Digilio et al, 2009] or due to de novo pure 16p13.3 duplications [Nruzinia et al, 2009].…”

A novel unbalanced translocation between the short arms of chromosomes 6 and 16 in a newborn girl: Clinical features and management

“…Terminal duplications of 16p that have been reported include 33 reports on 16p13.3 duplications and 100 reports on 16p13.11 duplications and these have been well described 1, 3…”