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A congenital muscular dystrophy characterized by autosomal recessive inheritance of muscular dystrophy with mental retardation and structural brain abnormalities that has material basis in homozygous or compound heterozygous mutation in the LARGE gene on chromosome 22q12.
Data assembled from 6 of 12 sources · Last updated Sep 20, 2026, 5:49 AM UTC
Online Mendelian Inheritance in Man
European rare disease database
Features include always present findings: Achilles tendon contracture, Elevated creatine kinase (muscle enzyme) (elevated circulating creatine kinase concentration), Profound intellectual disability, and Low muscle tone (hypotonia) and others. 29 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Muscles | 10 | Achilles tendon contracture, Low muscle tone (hypotonia), Generalized hypotonia |
Brain and nerves | 6 | Hypoplasia of the brainstem, Profound intellectual disability, Abnormal periventricular white matter morphology |
Arms and legs | 2 | Lower limb hyperreflexia, Joint contracture of the hand |
Bones and joints | 2 | Joint contracture of the hand, Skeletal muscle hypertrophy |
Head and neck | 1 | Facial palsy |
Lab test results | 1 | Elevated creatine kinase (muscle enzyme) (elevated circulating creatine kinase concentration) |
Growth and development | 1 | Short stature |
Eyes | 1 | Horizontal nystagmus |
Age of onset: infancy.
LARGE1 encodes LARGE xylosyl- and glucuronyltransferase 1 (756 aa). Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity. Highest expression in Colon Sigmoid (22.7 TPM) and Uterus (20.5 TPM).
Muscular dystrophy-dystroglycanopathy type B6 is associated with mutations in the LARGE1 gene on chromosome 22.
The LARGE1 protein participates in LARGE E669Gfs*26 pathway.
LARGE1 is classified as a druggable target (Enzyme category) with score 0.0.
Genetic testing for LARGE1 is available. Testing is considered confirmatory for diagnosis.
Phenotype severity distribution: 19 always present features.
No clinical trials have been registered for muscular dystrophy-dystroglycanopathy type B6.
1 publication has been identified in PubMed for muscular dystrophy-dystroglycanopathy type B6. Research spans Basic Science / Preclinical (100%).
Jahncke JN (2025). [PMID: 40473926](https://pubmed.ncbi.nlm.nih.gov/40473926/). *Communications biology*. [Basic Science / Preclinical]