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To date, less than 100 cases have been reported. There is no sex preference or particular ethnic preponderance.

Disease onset is typically in infancy and is non-progressive. Initial symptoms (from birth to 3 years) include lack of crying with trauma, self-mutilation (tongue, lips), swallowing and feeding problems. Gastroesophageal reflux is common. Sensory dysfunction is manifested by reduced or absent pain and temperature perception, and depressed or absent deep tendon reflexes. Corneal reflexes are reduced or absent. Muscle strength is preserved and there is no atrophy. Sensation to fine touch, position, vibration, taste, and gag reflexes may be diminished. Unrecognized injuries (e.g., burns, skin and corneal ulcers) and fractures of hands, feet, and limbs, sometimes resulting in osteomyelitis, as well as Charcot joints are frequent. Some patients have hearing loss. Autonomic involvement is limited to reduced lacrimation. Patients do not typically have orthostatic hypotension or sweating abnormalities.

Causal mutations in several genes have been identified and include SCN9A (2q24.3), WNK1 (12p13.33), RETREG1 (5p15.1), and KIF1A (2q37.3), all of which appear to be involved in the development of sensory nerves.

Diagnosis is based upon clinical features (congenital onset of severe reduction in sensory modalities and deep tendon reflexes resulting in injuries and self-mutilation). Neurophysiological evaluation (showing slow sensory conduction velocities and amplitudes), electromyogram and electroencephalographic studies support the diagnosis. Targeted genetic testing identifying described mutations in causatives genes is confirmatory. For cases in which no genetic mutation can be identified with targeted genetic testing, whole exome sequencing may identify novel variants/genes.

Differential diagnosis includes the other hereditary sensory and autonomic neuropathies, the most similar of which include hereditary sensory and autonomic neuropathy type 4 (characterized by complete lack of pain and complete lack of sweating), familial dysautonomia (accompanied by baroreflex abnormalities with paroxysmal episodes of nausea, retching, vomiting and hypertension) and hereditary sensory and autonomic neuropathy type 1 (typically adult-onset).

The pattern of inheritance is autosomal recessive. Where both parents are unaffected carriers, the risk of disease transmission to offspring is 25%. Offspring of affected individuals are obligate carriers. Penetrance is always complete, but the severity of the disease is variable.

Management is symptomatic and preventative. If feeding problems compromise nutrition and if gastroesophageal reflux is also present, fundoplication with gastrostomy might be considered. Parents' and patients' education is required to learn how to avoid injury and be alert for signs of unrecognized trauma. Reduced lacrimation requires artificial tears and corneal protective lenses to prevent corneal ulcers.

No natural history studies have been performed. Most patients reach adulthood.