Hereditary sensitive neuropathy type iiM89.8

Nélaton, 1852; Thévenard, 1942

Degeneration of the peripheral nerves of the posterior spinal cord roots of unknown cause with consecutive polyneuropathy and appearance of painless, deep ulcerations on feet and hands. The very rare HSN type II differs from HSN type I by the early onset of the clinical symptoms and the distinct involvement of the hands.

Autosomal recessive inheritance, low penetrance, variable expressivity.

In a first genotype (OMIM 210300), a mutation is present in the WNK1 gene, which is located on chromosome 12p13.33 and encodes WNK lysine deficient protein kinase 1.

In a second genotype (OMIM 613115), a mutation is present in the FAM14B gene, which is located on chromosome 2q37.3 and encodes reticulophagy receptor FAM134B.

In a third genotype (OMIM 614213), a mutation is present in the KIF1A gene, which is located on chromosome 2q37.3 and encodes kinesin-like protein KIF1A.

A fourth genotype (OMIM 2430000) has a mutation in the SCN9A gene, which is located on chromosome 2q24.3 and encodes sodium voltage-gated channel alpha subunit9.

Infant-infancy, male sex preferred.

Lower extremities; in contrast to HSN type I, the hands are stone covered.

Symmetrically arranged, stocking-shaped sensory disturbances for pain, temperature and touch, occasionally pyramid signs (Babinski positive). Often weakened tendon reflexes. Already in childhood painless ulcers, at first mostly on one side, later on both sides, especially in areas under pressure. Acrocyanosis and swelling of fingers and toes. Acroosteolyses, osteoporosis, possibly muscular atrophies, flat feet, splayfeet.

Hereditary sensitive neuropathy type I; syringomyelia, acropathia ulcero-mutilans non-familiaris, tabes dorsalis, leprosy, polyneuropathies (alcohol, diabetes mellitus, vitamin B1 deficiency).

Oysteomyelitis with risk of sepsis

Symptoms: Avoidance of local mechanical stimuli and pressure points (e.g. orthopaedic shoes), instruction for daily detailed self-examination for the smallest injuries, treatment of the ulcers with anti-infectious and wound healing promoting substances, see below wound treatment. Cooperation with neurologists and orthopaedic surgeons.

Slow progressive progression of clinical symptoms

1. Auer-Grumbach M et al (2003) Autosomal dominant inherited neuropathies with prominent sensory loss and mutilations: a review. Arch Neurol 60: 329-334
2. Auer-Grumbach M et al (2000) Ulcero-mutilating neuropathy in an Austrian kinship without linkage to hereditary motor and sensory neuropathy IIB and hereditary sensory neuropathy I loci. Neurology 54: 45-52
3. Bejaoui K et al (2002) Hereditary sensory neuropathy type 1 mutations confer dominant negative effects on serine palmitoyltransferase, critical for sphingolipid synthesis. J Clin Invest 110: 1301-1308
4. Bejaoui K et al (1999) Confirmation of linkage of type 1 hereditary sensory neuropathy to human chromosomes 9q22 Neurology 52: 510-515
5. Bockers M et al (1989) Persistent skin ulcers, mutilations, and acro-osteolysis in hereditary sensory and autonomic neuropathy with phospholipid excretion. Report of a family. J Am Acad Dermatol 21: 736-739
6. Gable K et al (2002) Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. J Biol Chem 277: 10194-10200
7. Child R (1976) On the syndrome of acroosteopathy ulcero-mutilans Thévenard. Z Hautkr 51: 927-932
8. Nélaton A (1852) Affection singulière des os du pied. Gazette des hôpitaux, (Paris) 4: 13
9. Thévenard A (1942) L'acropathie ulcéro-mutilante familiale. Rev Neurol (Paris) 74: 193-212