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IEMbase 0640: RXYLT1-related muscular dystrophy-dystroglycanopathy type A

Scope

Field Value
IEMbase ID 640
Nosology 18.2.1.01
Gene RXYLT1
External IDs OMIM:615041; ORPHA:51577
Generated mapping MAPPED; Lissencephaly_Spectrum_Disorders.yaml#Cobblestone
Candidate DisMech targets Better primary target: Dystroglycanopathy.yaml; phenotype-level target: Lissencephaly_Spectrum_Disorders.yaml#Cobblestone
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as autosomal recessive RXYLT1-CDG / muscular dystrophy-dystroglycanopathy with congenital brain and eye anomalies, type A.

Biochemical rows include markedly increased plasma creatine kinase from the neonatal period through adolescence, normal serum sialotransferrins, and an abnormal matriglycan-specific antibody readout across ages. Clinical rows emphasize optional cerebellar dysplasia, cobblestone lissencephaly, retinal dysplasia, intellectual disability, gonadal dysgenesis, and neonatal neural tube defect. Characteristic rows are hypotonia and muscular dystrophy.

DisMech phenotype coverage

The generated Lissencephaly_Spectrum_Disorders.yaml#Cobblestone match is a phenotype-level match, not a good disease-level target. That subtype captures cobblestone lissencephaly as a dystroglycanopathy-associated lissencephaly form, but it lists POMGNT1, POMT1, and POMT2 and does not model RXYLT1, CK elevation, matriglycan readout, muscular dystrophy, or the CDG/dystroglycan mechanism.

Dystroglycanopathy.yaml is the stronger local target. It includes an MDDG10 (RXYLT1) gene subtype, a type A severity subtype, defective alpha-dystroglycan O-mannosyl glycosylation, reduced matriglycan/laminin binding readouts, muscular dystrophy, elevated CK, cobblestone lissencephaly, intellectual disability, retinal dysplasia, seizures, hydrocephalus, and neonatal hypotonia.

Concordance and completeness

Judgement: locally covered at dystroglycanopathy-spectrum level, but the generated disease-level mapping is misleading.

DisMech captures the core RXYLT1 mechanism and most of the IEMbase type A phenotype signal if Dystroglycanopathy.yaml is used as the target. It does not yet provide a single explicit RXYLT1 type A cross-product subtype, and the RXYLT1-specific note is thinner than the general dystroglycanopathy mechanism. IEMbase-specific prompts not clearly captured locally include gonadal dysgenesis and neural tube defect.

Curation actions

  • Prefer Dystroglycanopathy.yaml over the lissencephaly-spectrum target for disease-level mapping.
  • Keep the lissencephaly cobblestone subtype as phenotype-level context only.
  • If row-level precision is needed, add or annotate an RXYLT1 / MDDG10 type A subtype under dystroglycanopathy.
  • Preserve RXYLT1, CK elevation, normal sialotransferrins, abnormal matriglycan antibody, hypotonia, muscular dystrophy, cobblestone/cerebellar/retinal, ID, gonadal, and neural-tube prompts.