SNP Shot: Genomic Insights

Emery-Dreifuss muscular dystrophy (EDMD) is a disease that primarily affects the muscles used for movement (skeletal muscles) and the heart muscle. One of the first signs of EDMD is joint stiffness, called contractures, which limits movement, especially in the elbows, ankles, and neck. These contractures usually appear in early childhood. Individuals with EDMD also experience progressive muscle weakness and wasting, initially affecting the upper arms and lower legs, and later spreading to the shoulders and hips.

Nearly all individuals with EDMD develop heart problems by adulthood. These problems often include irregularities in the heart's electrical system, leading to abnormal heartbeats (arrhythmias) and cardiac conduction defects. Without treatment, these issues can cause palpitations, a slow heartbeat (bradycardia), fainting (syncope), heart failure, and an elevated risk of sudden death.

Different forms of EDMD exist, classified by their inheritance patterns: X-linked, autosomal dominant, and autosomal recessive. Although the symptoms are generally similar across these types, a small percentage of people with the autosomal dominant form may only experience heart problems without any muscle weakness or wasting.

Inheritance:

EDMD can be inherited in several ways. When EDMD is caused by mutations in the EMD or FHL1 genes, it follows an X-linked recessive inheritance pattern. This means the mutated gene is located on the X chromosome. Males, with only one X chromosome, are more likely to be affected because only one altered copy of the gene is needed to cause the condition. Fathers with X-linked traits cannot pass them to their sons. Females, with two X chromosomes, usually need two altered copies of the gene to develop X-linked EDMD. While some female carriers (those with one altered copy) might not have muscle weakness or wasting, they may still develop heart problems or mild muscle weakness. In most cases of EDMD resulting from LMNA gene mutations, the condition follows an autosomal dominant inheritance pattern. This means only one altered copy of the gene is needed to cause the disorder. Around 65% of autosomal dominant EDMD cases arise from new mutations in the LMNA gene, with no prior family history. The remaining cases involve inheriting the altered LMNA gene from an affected parent. Rarely, EDMD caused by LMNA gene mutations can be inherited in an autosomal recessive manner. This means two altered copies of the gene are needed, one from each parent. The parents are usually carriers, possessing one copy of the altered gene but not showing symptoms of the disorder themselves.