Hereditary Neuropathy_CMT - isolated

Gene: MORC2

Green List (high evidence)

Charcot-Marie-Tooth disease type 2Z (CMT2Z) is an autosomal dominant axonal peripheral neuropathy characterized by onset, usually in the first decade, of distal lower limb muscle weakness and sensory impairment. The disorder is progressive, and affected individuals tend to develop upper limb and proximal muscle involvement in an asymmetric pattern, resulting in severe disability late in adulthood.

More than 10 unrelated families reported.

Heterozygous variants in MORC2 can also cause developmental delay, impaired growth, dysmorphic facies, and axonal peripheral neuropathy (DIGFAN; 619090), a more severe disorder with central nervous system involvement. These 2 disorders represent a phenotypic spectrum of nervous system abnormalities.

Created: 28 May 2021, 10:20 a.m. | Last Modified: 28 May 2021, 10:20 a.m.

Panel Version: 0.196

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Charcot-Marie-Tooth disease, axonal, type 2Z, MIM# 616688; MONDO:0014736

Publications

• 26497905
• 26659848
• 28771897
• 27105897

Red List (low evidence)

PMID: 32693025 - Reported in one 5 year old girl with spinal muscular atrophy (SMA) - like disease with neuropathy, cerebellar atrophy, and diaphragmatic paralysis (not CMT). This observation broadens the phenotypical spectrum of MORC2-related disorders towards SMA, spinal muscular atrophy with respiratory distress type 1 (SMARD1), and pontocerebellar hypoplasia.

Literature search - no additional evidence of association with SMA. Rated the gene as red for SMA.

Created: 3 Aug 2020, 6:22 a.m. | Last Modified: 3 Aug 2020, 6:22 a.m.

Panel Version: 0.3657

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spinal muscular atrophy

Publications

• PMID: 32693025