Clinical manifestations

Presentation and course

The patients with congenital presentation have nonprogressive, generalized weakness that delays walking until the age of 2 to 10 years. Most have significantly reduced muscle mass. Intellectual disability (IQs from 45 to 65) is also common. All have a normal creatine kinase level, EMG, and nerve conduction studies and are normal or consistent with a myopathy (08). Unlike most other congenital myopathies, a severe neonatal form of fingerprint myopathy has not been described. Also, in no cases has strength deteriorated to the point of necessitating aggressive orthopedic management. Muscles innervated by the cranial nerves are generally spared, although in one case, lower facial weakness and muscle wasting were quite prominent (08). However, the small number of reported cases prevents a more definite outline of the clinical course.

The reports of patients without neuromuscular signs or symptoms, and the rarity of reported cases, raise the possibility that fingerprint body myopathy may not be a distinct congenital myopathy. This is supported by the report of a child with fingerprint myopathy who on repeat muscle biopsy was found to have developed nemaline rods. In that individual, genetic testing identified two mutations in LMOD3, a gene usually associated with autosomal recessive nemaline myopathy (08).

Prognosis and complications

Most individuals with fingerprint myopathy have relatively mild weakness and remain ambulant, with a normal life expectancy (05; 01; 08). Although most reported cases have below-normal intelligence, more reports are required to verify or dispel the possibility that fingerprint body myopathy is generally associated with cognitive deficits.

Biological basis

Etiology and pathogenesis

The etiology of most cases of fingerprint myopathy is unknown. A report identified two LMOD3 mutations in an isolated case with congenital weakness (08).

Fingerprint bodies are subsarcolemmal, non-membrane bound inclusions, which are frequently adjacent to mitochondria. Their ultrastructural lamellar pattern produces a fingerprint-like appearance. The bodies usually are juxtaposed to myofibrils. Engel and associates noted no change in the ultrastructure following digestion with ribonuclease or glycerination (02). Although Sarnat was able to demonstrate the presence of desmin in several other congenital myopathies, a similar study has not been published of patients with fingerprint body myopathy (12). No postmortem cases are available.

Fingerprint bodies may derive from mitochondria (01) or be the consequence of abnormal muscle innervation (02).

Epidemiology

The number of reported cases is insufficient to predict the incidence of this condition. Muscle biopsy is not invariably diagnostic in children with congenital myopathies, and the diagnosis of fingerprint myopathy may well be missed if ultrastructural study is not undertaken.

The two reports of affected siblings strongly suggest a genetic basis for this condition, with the half-sibling relationship in one family suggesting an autosomal dominant pattern. The genetic basis of most cases of fingerprint myopathy is unknown, but one case was shown to have two mutations in LMOD3, a gene usually associated with nemaline myopathy.

Differential diagnosis

There are an increasing number of congenital myopathies with excessive protein aggregation, many of which have a defined genetic basis (04). These conditions include nemaline myopathy, minicore myopathy, and central core disease. In most cases the disease pathology is underpinned by either abnormal protein catabolism or genetic defects of sarcomeric protein formation and/or aggregation. In some cases, such as that described by Marguet and colleagues, muscle pathology can evolve on serial biopsies, such that the pathologic diagnosis may change over time, or changes typical of more than one condition may be seen on a biopsy. This clinical and pathologic overlap reflects the genetic heterogeneity of the congenital myopathies (04; 09; 08).

Fingerprint bodies have also been observed in a number of other myopathies, including myotonic dystrophy and oculopharyngeal muscular dystrophy (15; 07), as well as in patients suffering from neurodegenerative disorders (13).

Diagnostic workup

The decision to obtain a muscle biopsy should be based on the clinical picture: onset during infancy of a nonprogressive weakness with reduced muscle mass and a normal creatine kinase level, EMG, and nerve conduction velocity. Before the biopsy, instructions must be given to maintain a portion of muscle in glutaraldehyde for electron microscopy. If light microscopy reveals either normal tissue or type 1 predominance, an electron microscopy study should be considered.

In many centers, muscle biopsy is being largely superseded by next-generation genetic testing assessing the whole exome or a panel of genes known to cause myopathies.

Management

No treatment is available. It is possible that a wider range of motor and intellectual abilities may be present than the few reports indicate.

Special considerations

Anesthesia

There is a single report of malignant hyperthermia in an adult with fingerprint body myopathy. Pathologic findings in this case also included central cores and Z-line streaming. Malignant hyperthermia precautions are appropriate in patients with fingerprint body myopathy or a suspected congenital myopathy.