SNOMEDCT: 860810005; ORPHA: 970; DO: 0070150;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5p15.1 | Neuropathy, hereditary sensory and autonomic, type IIB | 613115 | Autosomal recessive | 3 | RETREG1 | 613114 |
A number sign (#) is used with this entry because hereditary sensory and autonomic neuropathy type IIB (HSAN2B) is caused by homozygous mutation in the FAM134B gene (RETREG1; 613114) on chromosome 5p15.
Hereditary sensory and autonomic neuropathy type IIB (HSAN2B) is an autosomal recessive neurologic disorder characterized by early childhood onset of distal sensory impairment usually resulting in ulceration and associated with variable autonomic features, such as hyperhidrosis and urinary incontinence. Some patients may show impaired gait (summary by Ilgaz Aydinlar et al., 2014).
HSAN2A (201300) is caused by mutation in the HSN2 isoform of the WNK1 gene (WNK1/HSN2; see 605232). For a discussion of genetic heterogeneity of HSAN, see HSAN1 (162400).
Kurth et al. (2009) reported 4 unrelated families with autosomal recessive inheritance of hereditary sensory and autonomic neuropathy. The families were from Saudi Arabia, Turkey, Italy, and Dubai; 2 families were known to be consanguineous. Onset occurred in the first or second decade, with impaired nociception and progressive mutilating ulceration of the hands and feet with osteomyelitis and acroosteolysis. Amputations of the hands and feet were common. Sensory function was severely impaired, and nerve conduction studies showed axonal sensory, and sometimes mild motor, neuropathy, primarily in the lower limbs. Sural nerve biopsies, when performed, confirmed axonal neuropathy. Autonomic dysfunction included hyperhidrosis, urinary incontinence, and slow pupillary light response. The phenotype was consistent with HSAN type II.
Ilgaz Aydinlar et al. (2014) reported 2 adult Turkish sibs, born of consanguineous parents, with early childhood onset of HSAN2B. The patients had delayed walking and painless foot ulcers in childhood. Examination as adults showed proximal and distal lower limb weakness and distal sensory impairment. Both also had a spastic gait. Autonomic features included urge incontinence, excessive sweating, and occasional orthostatic dizziness. Electrophysiologic studies showed a sensorimotor axonal neuropathy, and sural nerve biopsy showed loss of myelinating fibers.
The transmission pattern of HSAN2B in the families reported by Kurth et al. (2009) and Ilgaz Aydinlar et al. (2014) was consistent with autosomal recessive inheritance.
In affected members of 4 unrelated families with hereditary sensory and autonomic neuropathy type IIB, Kurth et al. (2009) identified 4 different homozygous truncating loss-of-function mutations in the FAM134B gene (613114.0001-613114.0004).
In 2 sibs, born of consanguineous Turkish parents, with HSAN2B, Ilgaz Aydinlar et al. (2014) identified a homozygous truncating mutation in the FAM134B gene (613114.0005). Functional studies of the variant and studies on patient cells were not performed.
Ilgaz Aydinlar, E., Rolfs, A., Serteser, M., Parman, Y. Mutation in FAM134B causing hereditary sensory neuropathy with spasticity in a Turkish family. (Letter) Muscle Nerve 49: 774-775, 2014. [PubMed: 24327336] [Full Text: https://doi.org/10.1002/mus.24145]
Kurth, I., Pamminger, T., Hennings, J. C., Soehendra, D., Huebner, A. K., Rotthier, A., Baets, J., Senderek, J., Topaloglu, H., Farrell, S. A., Nurnberg, G., Nurnberg, P., De Jonghe, P., Gal, A., Kaether, C., Timmerman, V., Hubner, C. A. Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nature Genet. 41: 1179-1181, 2009. [PubMed: 19838196] [Full Text: https://doi.org/10.1038/ng.464]