Retinal disorders

Gene: MORC2

Green List (high evidence)

Comment on list classification: As reviewed by Siying Lin, there are more than 3 individuals reported in literature with heterozygous MORC2 variants, presenting with syndromic retinal disease. The retinal phenotype ranged from mild pigmentary changes reported in childhood to severe retinitis pigmentosa in adulthood. Based on available evidence, this gene should be updated to Green for Retinal disease.

Created: 30 Jan 2026, 5:14 p.m. | Last Modified: 30 Jan 2026, 5:14 p.m.

Panel Version: 8.86

PMID: 39143067 Hanada et al., 2024
Report of a 56yo man with mild ID, distinctive facies, and history of muscle weakness; diagnosed with type 2 diabetes with nephropathy and retinopathy; heterozygous for c.1271 C > A, p.Thr424Lys.

PMID: 36791574 Stafki et al., 2023
Study of 8 individuals with MORC2 variants, with variable diagnoses: Cockayne syndrome, CMT, Cerebral palsy, and GDD. Retinal dystrophy was confirmed in 3 patients and suspected in 1 other. These individuals were heterozygous for de novo MORC2 variants: p.(Gly27Lys), p.(Ala88Val), p.(Arg132Cys).

PMID: 32693025 Sacoto et al., 2020
Cohort of 20 individuals with MORC2 variants. 5/6 patients who underwent dilated eye exams had retinal pigmentary abnormalities.
subject 5: 5yo female with p.Glu27Lys; syndromic presentation including retinal dystrophy on ERG
subject 6: 1yo female with de novo p.Glu27Lys; presented with hypotonia, hypertonia, GDD and non-specific peripheral retinal deposits
subject 10: male (6yo at examination) with de novo p.Arg132Cys; syndromic presentation, including subtle retinal pigmentary changes at age 7 years (?)
Subject 15: 9yo female with de novo p.Ser388Arg; syndromic, retinal phenotype: mild retinal changes with normal ERG; progressive hyperopia

PMID: 26659848 Albulym et al., 2016
Large Australian pedigree with 20 individuals affected by CMT. Two of the patients presented with CMT and additional mild pigmentary retinal changes and color perception abnormalities. Variant MORC2 c.754C>T, p.R252W segregated with disease.

https://doi.org/10.1111/ncn3.12660 Nomura et al., 2022
Japanese female patient with Charcot-Marie-Tooth type 2Z and severe retinitis pigmentosa. Patient harboured MORC2 c.754C>T, p.R252W. The patient presented with muscle weakness and walking disturbance in childhood. She showed night blindness and hearing loss at age 42 years, and she was diagnosed with RP. At age 48 years, she became completely blind in her right eye.

Additional evidence:
PMID: 40302207 Peymani et al., 2025: Pathogenic MORC2 variants cause a specific episignature, whereby methylation level variability and its repression impact on target genes (ERCC8, NDUFAF2 and FKTN) explains the pleiotropy and predicts phenotypic heterogeneity in MORC2-related disorders.

This gene is linked to AD Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy, 619090 and AD Charcot-Marie-Tooth disease, axonal, type 2Z, 616688 in OMIM (accessed 30th Jan 2026).

Created: 30 Jan 2026, 5:02 p.m. | Last Modified: 30 Jan 2026, 5:02 p.m.

Panel Version: 8.82

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy, OMIM:619090; Charcot-Marie-Tooth disease, axonal, type 2Z, OMIM:616688

Publications

• 26659848
• 32693025
• 36791574
• 39143067
• 40302207

Green List (high evidence)

PMID 32693025 - 5 out of 6 affected individuals who had dilated eye exams had retinal pigmentary abnormalities
PMID 36791574 - retinopathy seen in at least 3 out of 7 affected individuals
Sources: Literature

Created: 14 Jan 2026, 2:23 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Retinal dystrophy

Publications

• PMID: 36791574, 32693025

Mode of pathogenicity
Other