Ectodermal dysplasia‐like syndrome with mental retardation due to contiguous gene deletion: Further clinical and molecular delineation of del(2q32) syndrome

Abstract

We report on a patient with an interstitial deletion of the long arm of chromosome 2 at 2q31.2q33.2. She had prenatal and postnatal growth retardation, microcephaly, facial dysmorphism, cleft palate, camptodactyly, bilateral talipes equinovarus, severe intellectual disability, and ectodermal anomalies. She showed thin, atrophic skin, sparse, brittle, slowly growing hair, oligodontia with abnormally shaped teeth, normal sweating, and normal fingernails, consistent with a diagnosis of ectodermal dysplasia. Array CGH analysis (Agilent 44K) showed the deletion to span 26 Mb, between cytogenetic bands 2q31.2 and 2q33. The deletion leads to hemizygosity for the HOXD cluster and its regulatory elements, COL3A1/COL5A2, GTF3C3, CASP8, CASP10, and SABT2 could perhaps interfere with long range control of DLX1 and DLX2 expression. This girl confirms the existence of a clinically recognizable 2q32 microdeletion syndrome, as recently delineated by Van Buggenhout et al. and confirms a novel putative locus for ectodermal dysplasia on chromosome 2q31q33. We recommend considering cytogenetic and/or molecular screening for del(2q32) in patients with developmental disability and ectodermal dysplasia-like phenotype, including thin skin, oligodontia, dysplastic teeth, and sparse hair.

Deletion of 4.4 Mb at 2q33.2q33.3 May Cause Growth Deficiency in a Patient with Mental Retardation, Facial Dysmorphic Features and Speech Delay

“…To date, there are 27 reported patients with an interstitial deletion including the 2q33.1q33.3 region [Glass et al, 1989;Ramer et al, 1989Ramer et al, , 1990Rosenfeld et al, 2009;Urquhart et al, 2009;Rifai et al, 2010]. Only 2 carried deletions that did not include 2q33.1, the main band which is correlated with Glass syndrome according to the OMIM database ( fig.…”

Case series: 2q33.1 microdeletion syndrome--further delineation of the phenotype

“…The skin is reported to be similar to the wrinkly skin syndrome (WSS) and is suggested to be due to haploinsufficiency for COL3A1 and COL5A 3 6. However, other case reports of 2q32 microdeletions of these genes have alluded to thick hair and eyebrows in some patients 14 15.…”

“…Candidate genes deleted in patient 1 include CREB1 (OMIM *123810) and ADAM23 (OMIM *603710), which have been implicated as possible candidate genes in autism,17 18 and hyperactivity candidates ABI2 , CYP20A1 and ALS2 19. Other candidate genes for the neurologic phenotypes seen in individuals with deletions in this region include ZNF533 (180.01–180.43 Mb) and MYO1B (191.81–191.99 Mb), both of which are involved in neuronal function 6 14. The GLS gene (191.45–191.53 Mb) was also suggested as a candidate for the behavioural phenotype, as it is involved in glutamate production 14.…”

Critical region in 2q31.2q32.3 deletion syndrome: Report of two phenotypically distinct patients, one with an additional deletion in Alagille syndrome region

“…Standard cytogenetic analysis has revealed to date more than 30 reported cases presenting interstitial deletions involving region 2q31-q32, but with poorly defined breakpoints [1]. After the reports of Van Buggenhout et al .…”

“…Rifai et al . [1] and Cocchella et al . [5] reported two additional patients, with the last one refining a critical region for the syndrome and pointing out candidate genes to explain the phenotype.…”