Malformations of cortical development

Gene: MYCBP2

Green List (high evidence)

Comment on list classification: There are more than 3 unrelated individuals reported in literature with corpus callosum malformations and biallelic MYCBP2 variants. Hence, this gene can be promoted to Green at the next update.

Created: 1 Apr 2026, 4:37 p.m. | Last Modified: 1 Apr 2026, 4:37 p.m.

Panel Version: 7.50

PMID: 33875846 Bertoli-Avella et al., 2021
Large WES/WGS cohort. Study detected three de novo variants (one likely affecting splicing and two missense) in three patients with NDD, microcephaly, and seizures. One case presented bilateral bifid thumbs, talipes, and scoliosis, without vaginal or uterine anomalies. No variants details.

PMID: 36200388 AlAbdi et al., 2023
Eight patients (7 male, 1 female) with de novo MYCBP2 variants. Phenotypic spectrum: ID (4/8, moderate to severe), GDD (7/8), corpus callosum thinning / dysgenesis / agenesis (4/5). 2 patients had seizures and 1 had abnormal EEG; 1 patient diagnosed with cone dystrophy, one with retinopathy; 2 patients had hearing loss.

PMID: 41200582 Kostovska et al., 2025
Family with three affected members (mother and 2 sons aged 3yrs and 9 mo) carrying a novel heterozygous MYCBP2 variant NM_015057.5 c.7311del, p.(Leu2438Trpfs*3). Phenotypes: mild intellectual disability, dev delay, speech impairment, facial dysmorphism, microcephaly, seizures (only in the mother). Brain MRI not done.

PMID: 41543631 Pham et al., 2026
Proband with a maternally inherited c.4409dup (p.Leu1470Phefs*7), presented with global developmental delay, autism spectrum disorder (ASD), chronic constipation, sleep disturbances, and aggressive behaviors. Brain MRI showed normal corpus callosum. Mother had generally intact cognition (FSIQ = 103).

MYCBP2 is not yet associated with disease in OMIM (accessed 1st Apr 2026).
Sources: Literature

Created: 1 Apr 2026, 4:37 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 33875846
• 36200388
• 41200582
• 41543631