ClinVar Genomic variation as it relates to human health

The copy number loss of 14q32.31q32.33 largely overlaps the terminal region of 14q, deletions of which are associated with a recognizable 14q32.3 terminal deletion syndrome. The common clinical findings include growth delay, microcephaly, high forehead with lateral hypertrichosis, blepharophimosis, epicanthic folds, broad nasal bridge, high arched palate, single palmar crease, muscular hypotonia, congenital heart defects, genitourinary malformations, coloboma and mild to moderate developmental delay/intellectual disability (Ortigas et al., J Med Genet. 1997 Jun;34(6):515-7;. PMID: 9192277; van Karnebeek, et al., Am J Med Genet. 2002 Jun 1;110(1):65-72. PMID: 12116274; Maurin et al. Am J Med Genet A. 2006 Nov 1;140(21):2324-9. PMID: 17022077). More recent reports propose a small region critical for certain features of the terminal deletion 14q syndrome, along with multiple critical phenotype genes (Engels, et al., Am J Med Genet A. 2012 Apr;158A(4):695-706. PMID: 22367666. Holder, et al., Am J Med Genet A. 2012 Aug;158A(8):1962-6. PMID: 22488736). The proposed critical region and the critical genes of CRIP2, MTA1, and TMEM121 are encompassed by this copy number loss. Particularly , Youngs et al reported a similar 4.16 Mb deletion as the current case in a patient with developmental delay, hypotonia, and a particular face (Youngs et al., Clin Dysmorphol. 2011 Jul;20(3):143-7. PMID: 21358539). The present deletion also includes other genes associated with autosomal dominant OMIM phenotypes: DYNC1H1 (OMIM 158600, OMIM 614563, OMIM 614228), INF2 (OMIM 614455), PACS2 (OMIM 618067). Thus, the clinical significance of this deletion is pathogenic.