SNP Shot: Genomic Insights

Nemaline myopathy is a condition that primarily affects the skeletal muscles, the muscles responsible for movement. Individuals with this condition experience muscle weakness (myopathy) throughout their body. This weakness is usually most pronounced in the muscles of the face, neck, trunk, and proximal muscles (those closer to the body's center), like the upper arms and legs. The muscle weakness associated with nemaline myopathy can worsen over time. Those affected may experience difficulties with feeding and swallowing, foot deformities, an abnormal curvature of the spine (scoliosis), and joint deformities (contractures). While most individuals with nemaline myopathy are able to walk, some children may experience delays in starting to walk. Some individuals may eventually require the use of a wheelchair as the condition progresses. In severe instances, the muscles required for breathing can be affected, leading to life-threatening respiratory problems.

Nemaline myopathy is classified into six subtypes, ordered from most to least severe: severe congenital, Amish, intermediate congenital, typical congenital, childhood-onset, and adult-onset. These types are differentiated by the age of onset and the severity of symptoms, although there can be some overlap between them. The severe congenital type is the most life-threatening, with most affected individuals not surviving past early childhood due to respiratory failure. The Amish type is found exclusively in the Old Order Amish population of Pennsylvania and is typically fatal in early childhood. The typical congenital type is the most common form of nemaline myopathy and is characterized by muscle weakness and feeding problems that begin in infancy. Most individuals with this type do not experience severe breathing difficulties and are able to walk without assistance. The childhood-onset type usually results in muscle weakness beginning in adolescence. The adult-onset type is the mildest form of nemaline myopathy, with muscle weakness usually developing between the ages of 20 and 50.

Inheritance:

Nemaline myopathy is typically inherited in an autosomal recessive manner. This means that both copies of the responsible gene in each cell must have mutations for the condition to develop. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but usually do not exhibit signs or symptoms of the condition themselves. Less frequently, nemaline myopathy is inherited in an autosomal dominant manner, where only one copy of the altered gene in each cell is enough to cause the disorder. In many cases of autosomal dominant inheritance, the condition arises from new mutations in the gene and occurs in individuals with no family history of the disorder.