Hereditary and Sensory Autonomic Neuropathies

Dear Editor; We read with interest two recent papers on Congenital insensitivity to pain with anhidrosis, entitled " Congenital insensitivity to pain and anhydrosis (CIPA) syndrome; a report of 4 cases " by Daneshjou et al [1] and " Congenital insensitivity to pain with anhidrosis (HSAN type IV), extremely rare syndrome that can be easily missed by bone and joint surgeons: a case report " by Ali et al [2]. Although the clinical phenotypes of the cases are compatible with diagnosis of congenital insensitivity to pain with anhidrosis (CIPA), different presentations of the disease and lack of simple diagnostic tests makes CIPA a tricky diagnosis [3]. Thus making definite diagnosis should rest on genetic studies. Hereditary and Sensory Autonomic Neuropathies (HSAN) could be classified into five known subgroups: HSAN1A (OMIM #162400), inherited as an autosomal dominant trait, due to a mutation in the SPTLC1 gene (OMIM*605712), on chromosome 9q22.1-22, has an onset in the 2 nd to 4 th decade of life with slow and progressive distal sensory loss due to the dorsal ganglia degeneration and motor loss, leading to weakness and muscle wasting. The patient may complain of paresthesia, numbness, distal motor loss, and heel ulcers [4]. HSAN2A (OMIM #201300), inherited as an autosomal recessive trait, due to a mutation in the WNK1 gene (OMIM* 605232), on chromosome 12p13.33, has an onset in infancy and early years of life. No pain, thermal, touch, and pressure sensation is reported. Sensory loss has a pattern of glove and stocking, and the deep tendon reflex (DTR) is depressed in some patients. Skin biopsy shows involvement of large and small nerve fibers [4,5]. HSAN3 (OMIM#223900), also known as familial dysautonomia, or Riley Day syndrome, is inherited as an autosomal recessive trait, due to a mutation in the IKBKAP gene (OMIM*603722), on chromosome 9q31, and has an onset in infancy and early years of life. This syndrome presents with little or no sensation to pain and temperature, but normal touch sensation. Other features include recurrent gastrointestinal upsets, little lacrimation, anhidrosis, no sensation of tongue, depressed or no DTR, temperature flactuations, recurrent fractures, osteomyelitis, gait difficulties, Charcot joints, ligamentous laxicity, scoliosis, obvious lack of tong fungiform papillae, and no axon flare [4,6]. HSAN5 (OMIM#608654) is inherited as an autosomal recessive trait, due to a mutation in the NGFB gene (OMIM*162030), on chromosome 1p13. HSAN IV, also known as CIPA (OMIM #256800), is inherited as an …