ClinVar

Description

The copy number gain of 22q11.23 involves several protein-coding genes, including SMARCB1 (OMIM 601607) and SPECC1L (OMIM 614140). This copy number gain lies within the recurrent 22q11.2 distal LCR F-H duplication region. Copy number gains within this region have been reported in patients with developmental delay (DD) and other neurocognitive features. This genomic gain is a recurrent 22q11.2 distal LCR F-H duplication region. This type of gain has been reported in patients with developmental delay and other neurocognitive features. In a review of 30 cases, Pinchesfsky et al. reported that common features for duplications in this region include developmental delay (93%), neuropsychiatric features (26%), and nonspecific facial dysmorphisms (74%; Pinchesfsky 2017). In 70% of cases, the distal 22q11.2 duplications were inherited and many, but not all, of the carrier parents were phenotypically normal. Of note, many of the affected individuals had a concomitant variant. There are also reports of patients with overlapping duplications who have achygyria, seizures,hypotonia, impaired growth, esophageal atresia, tracheoesophageal fistula, optic nerve coloboma/dysplasia in optic nerve, and cardiac defects (Coppinger 2009, Nguyen 2017, Puvabanditsin 2015, Tan 2011, Valencia-Pena 2020, Wincent 2010). While there are several copy number gains of this region in the general populations of the Database of Genomic Variants, due to the reduced penetrance associated with this region, a pathogenic role for this copy number variant (CNV) cannot be ruled out. Thus, the clinical significance of this copy number variant (CNV) is likely pathogenic. References: Coppinger et al., Hum Mol Genet. 2009 Apr 15;18(8):1377-83. PMID:19193630Nguyen et al., Clin Case Rep. 2017 Feb 11;5(3):351-356. PMID: 28265405Pinchefsky et al., Child Neurol Open. 2017 Nov 1;4:2329048X17737651.PMID: 29147671Puvabanditsin S, et al., Genet Couns. 2015;26(3):313-20. PMID:26625662Tan et al. Am J Med Genet A. 2011 Jul;155A(7):1623-33., PMID:21671380Valencia-Pena et al., BMC Ophthalmol. 2020 Aug 17;20(1):333. PMID:32807111Wincent et al., Mol Syndromol. 2010;1(5):246-254., PMID: 22140377