The plantar ulcer overlying the head of a metatarsal bone is the most dreaded complication, because it often leads to osteomyelitis. Infection of the pulp of the fingers and paronychias are uncommon. Some patients have a mild pes cavus and weakness of the peroneal and pretibial muscles, with foot-drop and steppage gait. Lancinating pains may occur in the legs, thighs, and shoulders, and, exceptionally, the pain may last for days or longer and be as disabling as that of tabes dorsalis; however, in the majority of patients there is no pain whatsoever. Neural deafness was present in one of Denny-Brown’s patients. In that case, which was studied postmortem, there was a loss of small nerve cells in the lumbosacral dorsal root ganglia; the dorsal roots were thin, and the fibers in the posterior columns of the spinal cord and those in the peripheral nerves were diminished in number. Myelinated and unmyelinated fibers were both affected. Both axonal degeneration and segmental demyelination have been demonstrated in teased nerve preparations. Sensory nerve conduction may be absent or is uniformly slowed in every nerve tested.
It must be emphasized that despite its categorization as a “sensory and autonomic neuropathy,” the most common, dominantly inherited form, termed HSAN1, also entails progressive, disabling, distal motor weakness, a consequence of ongoing axonopathy and denervation. HSAN1 is a consequence of a loss of function of the enzyme serine palmitoyltransferase, which is the rate-limiting step in the biosynthesis of sphingolipids.
Recessive Mutilating Sensory Polyneuropathy of Childhood
Here the pattern of inheritance is autosomal recessive. Onset is in infancy and early childhood and walking is delayed; there is pes cavus deformity and the first movements are ataxic. Ulcerations of the tips of toes and fingers and repeated infections of these parts result in the formation of paronychias and whitlows. The tendon reflexes are absent, but power is well preserved. All sensory modalities are impaired (touch-pressure somewhat more than pain-temperature), mainly in the distal parts of the limbs but also over the trunk. In addition, there are reports of several sibships in which multiple members had a sensory neuropathy manifest by a generalized insensitivity to pain of the type described later. The lesions and electrophysiologic findings are similar to those in the dominantly inherited sensory neuropathy described previously.
In all types of hereditary sensory neuropathies, measures must be taken to prevent stress fractures, acral mutilation, and infection. This is more difficult in the small child who does not understand the problem.
It is also now evident that some of the infantile hereditary sensory neuropathies are a result of a disruption of molecular signaling pathways for neurotropic substances, such as nerve growth factor, that are critical to neural development.
Congenital Insensitivity to Pain