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IEMbase 0353: POMT2-related muscular dystrophy-dystroglycanopathy

Scope

Field Value
IEMbase ID 353
Nosology 18.2.02.02
Gene POMT2
External IDs OMIM:613150; OMIM:613156; OMIM:613158; ORPHA:899
Generated mapping UNMAPPED; low candidate Dystroglycanopathy.yaml
Candidate DisMech targets Dystroglycanopathy.yaml#MDDG2/POMT2
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents POMT2-CDG/muscular dystrophy-dystroglycanopathy type A2, type B2, and type C2, an autosomal recessive O-mannosylation disorder. Characteristic rows include buphthalmos, cerebral cortical malformations, increased creatine kinase, glaucoma, megalocornea, microphthalmia, muscular dystrophy, pigmentary retinopathy, psychomotor delay, normal sialotransferrins, and Walker-Warburg syndrome.

Additional clinical rows include corpus callosum agenesis on MRI, cataract, cerebellar abnormalities, cobblestone lissencephaly, dysmorphic features, encephalocele, epilepsy, exophthalmia, fatal evolution before 1 year, and hydrocephalus. Biochemical rows include creatine kinase, matriglycan-specific monoclonal antibody, and sialotransferrins. No treatment rows are present.

DisMech phenotype coverage

The generated UNMAPPED status is a false negative. DisMech has a Dystroglycanopathy file that explicitly covers muscular dystrophy-dystroglycanopathy types A/B/C and the POMT2/MDDG2 subtype. Local mechanism describes defective O-mannosyl glycosylation of alpha-dystroglycan; POMT2 forms the POMT1-POMT2 enzyme complex required for the first O-mannosylation step and can produce the full type A/B/C severity spectrum.

Local coverage includes muscular dystrophy, proximal weakness, neonatal hypotonia, elevated serum CK, cobblestone lissencephaly, intellectual disability, retinal dysplasia, hydrocephalus, seizures, reduced alpha-dystroglycan glycosylation, reduced laminin binding, supportive rehabilitation, genetic counseling, and emerging ribitol/AAV therapeutic context.

Concordance and completeness

Judgement: false negative; resolve to the local dystroglycanopathy POMT2 subtype.

The resources agree on POMT2 identity, autosomal recessive inheritance, O-mannosylation/alpha-dystroglycan biology, Walker-Warburg/type A severe spectrum, muscular dystrophy, elevated CK, cortical/cobblestone brain malformations, hydrocephalus, seizures, ocular involvement, psychomotor delay, and early lethality in the severe end.

Curation actions

  • Map this record to Dystroglycanopathy.yaml, specifically the POMT2/MDDG2 subtype context.
  • Consider future enrichment with buphthalmos, megalocornea, microphthalmia, cataract, glaucoma, pigmentary retinopathy, corpus callosum agenesis, encephalocele, fatal-before-1-year wording, and matriglycan antibody testing after source verification.
  • Treat absent IEMbase treatment rows as incomplete IEMbase coverage rather than a contradiction of local supportive and investigational therapy context.