Strong Genetic

Limb-Girdle Muscular Dystrophy Type 2E (LGMDR4)

GeneSGCBrsIDrs121908099InheritanceAutosomal recessiveCarrier frequency~1 in 15 in Indiana Amish (S114F founder), rare in general populationSystemCarrier Screening

Summary

LGMD2E (LGMDR4) is a progressive muscular dystrophy caused by beta-sarcoglycan deficiency. Clinical presentation is similar to LGMD2D — progressive proximal weakness beginning in childhood. However, LGMD2E tends to have a more severe course with earlier cardiac involvement. Dilated cardiomyopathy is a significant concern and can be the most life-threatening aspect. Respiratory failure may develop.

Practical takeaway

Particularly relevant if your partner is of Amish descent. Carrier testing is available. Realised does not calculate reproductive risk or advise on reproductive decisions.

Evidence detail

What Carrier Status Means For You

You are not affected. One working copy of SGCB is sufficient. Standard 25/50/25 recessive inheritance applies.

Population Context

The S114F variant is enriched in the Indiana Amish community through a founder effect. LGMD2E occurs in all populations due to diverse SGCB variants, but at much lower frequencies outside the Amish.

Limitations

23andMe tests 1 SGCB variant. Coverage limited to the Amish founder mutation. Comprehensive LGMD panels recommended for broader testing.

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