Chromosome 8q21.11 Deletion Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome.

Description

The chromosome 8q21.11 deletion syndrome is characterized by intellectual disability and common facial dysmorphic features (summary by Palomares et al., 2011).

Clinical Features

Palomares et al. (2011) reported 8 unrelated individuals with intellectual disability and common facial dysmorphic features who had an overlapping heterozygous microdeletion involving chromosome 8q21.11 (See CYTOGENETICS). Dysmorphic features were variable and included round face with full cheeks, a high forehead, ptosis, corneal opacities, wide nasal bridge, underdeveloped alae, a short philtrum, a cupid's bow of the upper lip, downturned corners of the mouth, micrognathia, low-set and prominent ears, and short neck. Many had mild finger and toe anomalies, such as camptodactyly, syndactyly, and broadening of the first rays. Most also had hypotonia. Two had impaired balance, 3 had sensorineural hearing loss, 3 had underdeveloped corpus callosum, and 2 had unusual behavior.

Cytogenetics

Palomares et al. (2011) reported 8 unrelated patients with an overlapping heterozygous deletion at chromosome 8q21.11 detected by cytogenetics, array comparative genomic hybridization, FISH, multiplex ligation analysis, and/or microsatellite analysis. High-density targeted oligonucleotide array showed that all 8 had overlapping deletions ranging in size from 0.66 to 13.55 Mb with a minimal region of 539.77 kb (chr8:77,226,464-77,766,239, GRCh37). One patient had a complex rearrangement consistent with 2 deletions close to one another and involving 8q21. All of the deletions were of a different size and had different breakpoints. The minimal region of overlap included the ZFHX4 gene (606940), a microRNA of unknown function (LOC100192378), and a nonfunctional pseudogene (MRPL9P1). Seven of the 8 patients also had heterozygous deletions of PEX2 (170993). Loss of ZFHX4, which is expressed in human brain, muscle, and liver (Hemmi et al., 2006), may be a candidate for the disorder, but Palomares et al. (2011) noted that a patient with a translocation disrupting the ZFHX4 gene reported by McMullan et al. (2002) did not have intellectual disability or unusual morphologic features other than isolated ptosis (see 178300).