15q13.3 recurrent region (BP4-BP5) (includes CHRNA7)

Sharp et al. (2008) reported six unrelated probands (along with three affected carrier family members; total of nine patients) with deletion of the 15q13.3 (BP4-BP5) region. Clinical findings in common across patients included developmental delays, intellectual disability, and dysmorphic features. Some patients also had a history of seizures, hypotonia, or abnormal EEG. Inheritance was known for 4 individuals: two probands had de novo deletions and two inherited the deletion from an affected parent. Both mothers and a sibling that carried the deletion were clinically affected. No deletions were identified in the 960 controls screened (p=0.005).

Ben-Shachar et al. (2009) reported clinical findings of 12 families (14 children and six parents; total of 20 individuals) with deletion of the 15q13.3 region identified through routine array testing; 11 families with 15q13.3 (BP4-BP5) deletion and one with a BP3-BP5 deletion. Phenotypes in the children included developmental delay, intellectual disability, ASD, speech delay, aggressiveness, ADHD, and other behavioral problems. Facial appearances ranged from normal to moderately dysmorphic. Epilepsy was observed in only one of 14 children and in none of the parents. Inheritance was known for seven probands: one deletion was de novo and six were inherited. Two fathers with the deletion had learning disabilities and bipolar disorder; the other four parents with the deletion were clinically unaffected.

Helbig et al. (2009) identified 11 unrelated probands with 15q13.3 (BP4-BP5) deletions and one patient with a BP3-BP5 deletion from a combined cohort with idiopathic generalized epilepsy (GE). Comparison of clinical findings to those reported originally for the 15q13.3 microdeletion syndrome showed notable differences: only three probands had intellectual disability, 9 did not have dysmorphic features or intellectual disability. Inheritance was known for 5 individuals: one deletion was de novo and four were inherited. One carrier parent was described as having a panic disorder while the other carrier parents were clinically unaffected. Siblings that carried the deletion had epilepsy or intellectual disability. The frequency of 15q13.3 deletions was compared to ancestrally matched controls; altogether, 15q13.3 deletions were observed in 12/1223 cases and in 0/2669 controls (p=5.32E-8). The authors suggest there is “…extensive variability in the phenotypic manifestation associated with 15q13.3 deletion…”