Chromosome 11p13 Deletion Syndrome, Distal

A number sign (#) is used with this entry because of evidence that the phenotype results from a contiguous gene deletion of chromosome 11p13 including the ELP4 (606985) and PAX6 (607108) genes.

The deleted region is distal to that involved in the WAGR syndrome (194072). Mutation in the PAX6 gene can cause congenital eye malformations, including aniridia (AN; 106210).

Clinical Features

Addis et al. (2015) reported 24 patients with a range of neurodevelopmental disorders associated with heterozygous copy number variants (CNVs; 23 deletions and 1 duplication) involving the ELP4 gene on chromosome 11p13. Most had developmental delay with intellectual disability and speech and language disorder. Several had autism or autistic features, including 6 with a primary diagnosis of autism. Several patients had congenital eye malformations.

Cytogenetics

Addis et al. (2015) provided evidence that heterozygous deletions of the ELP4 gene on chromosome 11p13 may contribute to a range of neurodevelopmental disorders, including general developmental delay, speech and language disorders, and autism spectrum disorders. In the first stage of their study, array CGH testing found that 8 of 4,092 individuals referred for neurodevelopmental disorders had small (less than 1 Mb) deletions disrupting the ELP4 gene. A ninth patient had a 232-kb duplication of the first 7 exons of ELP4 and the PAX6 gene. Four of the patients had CNVs affecting other chromosomes. Only 1 CNV, a microdeletion, involving the ELP4 gene was found in the WTCCC control set of 4,783 individuals (p = 7.5 x 10(-3)). In the second stage of the study, 9 of over 10,000 individuals from the DECIPHER database carried a small (less than 1 Mb) deletion encompassing the ELP4 gene. The phenotype of these individuals included developmental delay, intellectual disability, speech delay, and autism spectrum disorder. Several patients with deletions that disrupted the PAX6 gene or that disrupted a PAX6 enhancer region in intron 9 of the ELP4 gene had congenital eye malformations, such as aniridia. In the third stage of the study, 6 patients with autism from 2 cohorts totaling over 3,000 patients were found to have deletions involving the ELP4 gene. No CNVs involving the ELP4 gene were found in 6,469 controls (p = 2.7 x 10(-3)). In the study overall, the deletions ranged in size from 26 kb to 600 kb, there were no recurrent breakpoints, and several patients had deletions that involved other neighboring genes, including IMMP1L (612323), DCDC1 (608062), and DNAJC24 (611072). In addition, the CNVs were inherited from a presumably unaffected parent in 14 of 24 cases, indicating that the genetic model is clearly not monogenic. Addis et al. (2015) concluded that disruption of the ELP4 gene may contribute to a range of neurodevelopmental phenotypes. No functional studies or studies on patient cells were performed.