Family History
Suspicion of a neuromuscular disease warrants the ascertainment of a detailed family history and pedigree chart. Autosomal-dominant conditions may have pedigrees with multiple generations affected, with equal predilection to males and females.
Typically, one-half of offspring within a pedigree are affected. In autosomal-recessive conditions, only one generation may be affected, with equal proportions of males and females. Proportionally, one-fourth of offspring are clinically affected. Parents in earlier generations may be normal, and the parents of affected children are presumptive heterozygote carriers of the condition. In many instances of autosomal-recessive inheritance, no other family members within the nuclear family unit are affected, making the confirmation of inheritance pattern difficult without a molecular genetic marker present or protein abnormality confirmed by immunohistochemistry techniques. In X-linked recessive conditions, males on the maternal side of the family are affected in approximately 50% of instances and females are carriers in 50% of instances.Often, it is valuable to examine affected relatives who may be either earlier or later in the course of their neuromuscular disease relative to the affected child. In addition, medical records and diagnostic evaluations of affected family members should be reviewed and the diagnosis confirmed if possible. In some instances, the examination of a parent can help establish the diagnosis in an affected infant or child, as is frequently the case in myotonic muscular dystrophy 1 (MD1). In this disorder, genetic anticipation with abnormal CTG trinucleotide expansion of unstable DNA results in progressively earlier onset of the disease in successive generations with increasing severity.
In the case of dystrophic myopathies, a definitive molecular genetic or pathologic diagnosis, established in a sibling or close relative, may allow the clinician to establish the diagnosis in a child or adult based on clinical examination, easily obtained laboratory data such as creatine kinase, or molecular genetic testing, thus allowing the avoidance of further invasive testing such as muscle biopsy.