15q24 recurrent region (LCR C-LCR D) (includes SIN3A)

Witteveen et al. (2016), reported 3 patients with 15q24 LCRC-D deletions. These patients presented with developmental delay, intellectual disability, structural brain anomalies, microcephaly, dysmorphic craniofacial features, thin hair, hypermobile joints, and additional clinical findings. The dysmorphic craniofacial features were variable, with the recurrent features including downslanting palpebral fissures, deep set eyes, small mouth, and a pointed chin. Parental testing showed that each of these deletions was de novo. A fourth individual with a deletion in this region was reported by this group (Patient 4); however, the distal breakpoint for that patient's deletion was proximal to 15q24 LCRD. The clinical findings in Patient 4 were similar to those with breakpoints in LCRD including developmental delay, downslanting palpebral fissures, small mouth, and a pointed chin. The deletion in patient 4 was also found to be de novo. The authors of this paper also report nine patients (from five families) with loss-of-function type variants in SIN3A, which lies within the 15q24 LCRC-D region. These patients presented with similar clinical findings to the patients with 15q24 LCRC-D deletions.

Mefford et al. (2012) reported one patient (Patient 14) with a 15q24 LCRC-D deletion. This patient presented with borderline mild intellectual disability, short stature, structural brain abnormalities, possible Asperger, telecanthus, bilateral epicanthi, hypermobile joints, and bilateral short 5th fingers. The deletion in this patient was found to represent a de novo event. The authors also reported a second individual (Patient 13) with a smaller de novo deletion within the 15q24 LCRC-D region; however, the distal breakpoint for that patient’s deletion was proximal to 15q24 LCRD. That patient was reported to have mild intellectual disability, developmental delay (speech and motor), obsessive compulsive behaviors, microcephaly, a round face, short 5th metacarpals, toe syndactyly, and additional clinical findings.