In 1926, Roussy and Lévy reported 7 cases of a dominantly inherited ataxic and neuropathic malady that had not previously been described. Its close relation to Friedreich ataxia and the amyotrophy of Charcot-Marie-Tooth disease was recognized. On the basis of molecular genetic testing, these relationships been clarified. Most classifications group it with CMT1 on the basis of the causative mutations and nerve conduction studies.
The condition is a sensory ataxia with pes cavus and areflexia, affecting mainly the lower legs and progressing later to involve the hands. Some degree of sensory loss, mainly of vibratory and position sense, is described in all cases. Atrophy of the muscles of the legs and postural tremor eventually become prominent, but the patients do not have signs of cerebellar disease (dysarthria, tremor, nystagmus). Kyphoscoliosis, a feature typical of Friedreich disease, has been described in several cases. Although the feet may be cold or slightly discolored, no autonomic defects are documented and the nerves are not palpably enlarged. Electrocardiographic abnormalities similar to those of Friedreich ataxia have been noted in one family but are not usual. The onset in many patients is during infancy, possibly dating from birth, and the course is relatively benign; all descendants of the original Roussy-Lévy family were still able to walk during their seventh decade of life.
On clinical and pathologic grounds, Dyck and
Lambert (1975) placed the Roussy-Lévy kinships within the category of the demyelinating type of Charcot-Marie-Tooth disease (CMT1). The mode of inheritance of the 2 syndromes, their benign course, pattern of neurologic signs, slow nerve conduction, and biopsy features (demyelination of nerve fibers with onion-bulb formation) are much the same. This view has been reinforced by the genetic findings reported by Planté-Bordeneuve and colleagues. In affected members of the original Roussy-Lévy family, these investigators identified a point mutation in the domain of the myelin protein gene PO, the same gene that is implicated in Dejerine-Sottas disease. Most currently studied cases (there are few) have point mutations in PMP22 or MPZ. Based on limited pathologic study, there is no cerebellar degeneration; nevertheless, the shared clinical features with Friedreich ataxia are unmistakable and create diagnostic confusion before genetic testing.
Polyneuropathy With Cerebellar Degeneration (See “Predominantly Cerebellar Forms of Hereditary and Sporadic Ataxia” in Chap. 38)
Several such cases of adult onset have come to our attention over the years. Unlike Friedreich disease, the ataxia is mild and there is no kyphoscoliosis, but pes cavus or hammer-toe deformities are found, attesting to the early onset of the neuropathy. The lower legs become atrophic and findings characteristic of CMT such as absent ankle reflexes and mild to moderate loss of distal deep sensibility are present. There is no Romberg sign and no Babinski signs. The outstanding feature is a profound atrophy of the cerebellar hemispheres, and to some extent of the vermis, on MRI. Although the illness is slowly progressive, our patients, like those with Roussy-Lévy disease, have remained highly functional into late age, having difficulty mostly with maintaining balance when dancing or wearing high-heeled shoes. The EMG is consistent with CMT2. The electrocardiogram has been normal. Several, but not all, such patients have had a family history of a similar process, but the available genetic testing has failed to reveal the site of a mutation. As mentioned, the process can simulate Friedreich ataxia in some respects. The genetic basis is uncertain and various genotypes have been reported in single families.