Motor sensory neuropathy with minifascicle formation in a woman with normal karyotype

Minifascicle neuropathy (MN) is a rare developmental malformation of the peripheral nerve characterized by many small fascicles.1 Two unrelated cases, in which the disorder was associated with 46XY pure gonadal dysgenesis (GD),have been reported. We report a 28-year-old woman with healthy unrelated parents. Neurologic examination suggested hereditary motor-sensory polyneuropathy (HMSN): difficulty in walking with bilateral stepping; weakness and hypotrophy of the distal muscles of the four limbs, especially tibialis anterior; reduced superficial sensation; more accentuated distally and absent deep tendon reflexes. EKG showed sinus bradycardia. Gynecological and pelvic ultrasound examinations were normal; sexual characteristics and 46XX caryotype were both normal. MN is described as an entity in its own right, unrelated to the above causes, in two patients with motor-sensory polyneuropathy and XY pure GD, in only one of whom a homozygous mutation in the DHH gene was found.Neither patient had mutation in the SRY gene, which is often involved in GD. In the present case, we failed to detect any mutations in DHH, SRY, PMP22, P0, or EGR2 genes. As in the previously reported cases, our biopsy findings suggested axonal neuropathy; however, in the above cases, the fascicles were more numerous, smaller, and with more evident structural disorganization (microfasciculation). The most remarkable difference was that minifascicle neuropathy was not associated with XY GD in our case. We suggest that HMSN syndromes with MN may exist independently of XY GD, caused by unidentifield genes involved in perineurial differentiation