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Hereditary sensory and autonomic neuropathies
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Hereditary sensory and autonomic neuropathies

Contributors: William Farmer MD, Keith Morley MD, Susan Burgin MD, Eric Ingerowski MD, FAAP
Other Resources UpToDate PubMed

Synopsis

Hereditary sensory and autonomic neuropathies (HSANs) are inherited peripheral neuropathies with variable expressivity often presenting in childhood and early adulthood. They are caused by the loss of large myelinated and unmyelinated fibers leading to self-mutilation, peripheral sensory loss, and autonomic dysfunction. HSANs have been classified into at least 8 different disorder types based on their genetic and clinical findings. Some children do not fall well into this classification system. While penetrance of most HSANs is complete, expression is variable.

HSAN type 1, also known as hereditary sensory radicular neuropathy, is divided into 6 subtypes based on the gene of inheritance. These are mostly autosomal dominantly inherited, and onset occurs in early adulthood. HSAN type 1 is associated with distal sensory loss, foot ulcers, preservation of facial sensation, muscle wasting, muscle weakness, neural deafness, and dementia.

HSAN type 2, also known as congenital sensory neuropathy (CSN), is autosomal recessively inherited and has 4 subtypes. It is characterized by the loss of temperature, pain, and tactile sensations, especially in the fingers and toes, leading to recurrent infection and fractures. It is seen at birth with symptoms that may include swallowing problems, self-mutilation, developmental delay, lack of fungiform papillae, hearing loss, absent pain perception, depressed deep tendon reflex, gastroesophageal reflux (GERD), and scoliosis.

HSAN type 3, also known as familial dysautonomia (FD) or Riley-Day syndrome, is an autosomal recessively inherited disorder caused by a mutation of the IKBKAP gene. This disorder occurs at birth, and symptoms may include swallowing problems, aspiration pneumonia, hypothermia, developmental delay, lack of fungiform papilla, absent lacrimation, depressed deep tendon reflexes, GERD, postural hypotension, episodic hypertension, blotchy erythema and mottling of the skin, and scoliosis. Affected individuals have episodes of dysautonomic crises triggered by physical or emotional stress with nausea, vomiting, hypertension, tachycardia, facial flushing, irritability, and swallowing and speech dysfunction. Other features of autonomic dysfunction include orthostatic hypotension, excessive salivation, gastrointestinal motility dysfunction, bladder dysfunction, and abnormal pupil dilation. HSAN type 3 almost exclusively occurs in the Ashkenazi Jewish population.

HSAN type 4, also known as congenital insensitivity to pain with anhidrosis (CIPA), is an autosomal recessively inherited mutation of the NTRK1 (TRKA) gene that causes profound loss of pain and temperature sensitivity that can lead to self-mutilation, especially of the face and mouth, fractures, and osteomyelitis. Anhidrosis and thermodysregulation lead to recurrent fevers. Microcephaly and mild mental retardation may be present. Tearing is preserved, and fungiform papillae are present on the tongue. Fifty percent of individuals with HSAN type 4 are the result of a consanguineous union.

HSAN type 5 is caused by a mutation in the NGFB gene that causes congenital insensitivity to pain and temperature sensations with partial anhidrosis. Other sensations are preserved. Self-mutilation of the mouth, nose, ears, eyes, and digits are common. Individuals may have bite wounds and ulceration on their tongue as well as autoextraction of multiple teeth.

HSAN type 6 is an autosomal recessively inherited disorder due to a mutation of the DST gene. It is characterized by neonatal hypotonia, psychomotor dysfunction, respiratory dysfunction, feeding dysfunction, absent fungiform papillae, and areflexia including lack of corneal reflex, which leads to corneal scarring. Death typically occurs by the age of 2 years.

HSAN type 7 is an autosomal dominantly inherited disorder due to a mutation in the SCN11A gene. Congenital insensitivity to pain leads to self-mutilation, fractures, slow wound healing, gastrointestinal dysfunction, hyperhidrosis, mild muscle weakness, and delayed motor development.

HSAN type 8, also known as midface toddler excoriation syndrome (MiTES), has been described in several young children with erosions in a bilateral distribution localized to the midface. Habitual scratching initiates around the first year of life, leading to deep, chronic, scarring wounds around the nose and eyes. Reports describe developmental delay and seizures. Most of these cases have been linked to homozygous recessive mutations of the PRDM12 gene.

For more information, see OMIM.

Codes

ICD10CM:
G60.0 – Hereditary motor and sensory neuropathy

SNOMEDCT:
128205005 – Hereditary sensory and autonomic neuropathy

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Last Reviewed:12/05/2019
Last Updated:07/01/2020
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Hereditary sensory and autonomic neuropathies
Hereditary sensory and autonomic neuropathies (Type 1) : Areflexia, Muscle weakness, Muscle wasting
Copyright © 2021 VisualDx®. All rights reserved.