Hereditary sensory neuropathy type 1

Alternate names

HSAN 1; Neuropathy hereditary sensory radicular, autosomal dominant; Neuropathy hereditary sensory and autonomic type 1; HSN1; Hereditary sensory and autonomic neuropathy type 1

Definition

Hereditary sensory neuropathy type 1 (HSN1) is a neurological condition characterized by nerve abnormalities in the legs and feet.

Onset

Symptoms of HSN1 typically begin during a person's teens or twenties and worsen over time.

Cause

At least four genes responsible for hereditary sensory neuropathy type 1 (HSN1) have been found:

• HSN1A (the most common form) is associated with mutations in the SPTLC1 gene
• HSN1B, reported in a small number of families, is linked to a specific location on chromosome 3, but the exact gene has not yet been identified
• HSN1C is caused by mutations in the SPTLC2 gene
• HSN1D is caused by mutations in the ATL1 gene (the same gene is associated with early-onset hereditary spastic paraplegia 3A)
• HSN1E is caused by mutations in the DNMT1 gene.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Hereditary sensory neuropathy type 1 (HSN1) is inherited in an autosomal dominant manner. This means that having only one changed (mutated) copy of the responsible gene in each cell is enough to cause signs and symptoms of the condition. When a person with an autosomal dominant condition has children, each child has a 50% (1 in 2) risk to inherit the mutated gene from the affected parent. In rare cases, a mutation that causes HSN1 occurs sporadically as a new (de novo) mutation in a person without an affected parent.

Signs and symptoms

Many people with this condition have tingling, weakness, and a reduced ability to feel pain and sense hot and cold. Some affected people do not lose sensation, but instead feel shooting pains in their legs and feet. As HSN1 progresses, sensory problems can affect the hands, arms, shoulders, and abdomen. In rare cases, people with this condition develop sensorineural hearing loss.

Diagnosis

At least four genes responsible for hereditary sensory neuropathy type 1 (HSN1) have been found:

• HSN1A (the most common form) is associated with mutations in the SPTLC1 gene
• HSN1B, reported in a small number of families, is linked to a specific location on chromosome 3, but the exact gene has not yet been identified
• HSN1C is caused by mutations in the SPTLC2 gene
• HSN1D is caused by mutations in the ATL1 gene (the same gene is associated with early-onset hereditary spastic paraplegia 3A)
• HSN1E is caused by mutations in the DNMT1 gene.

Although the genes for some other types of HSN1 have been identified, we are not aware of clinical laboratories that offer genetic testing for them. A genetics professional may be able to help you locate laboratories that offer testing for other types of HSN1.

The diagnosis of SPTLC1-related HSN is established in a proband with characteristic clinical features and identification of a heterozygous pathogenic variant in SPTLC1 on molecular genetic testing.

SPTLC1-related hereditary sensory neuropathy (HSN) should be suspected in individuals with the following clinical findings and family history:

• Initial sensory neuropathy that then becomes a motor and sensory axonal neuropathy
• Painless injuries in the feet and hands with skin ulceration, Charcot joints, sometimes amputations
• Distal muscle weakness that spreads proximally producing limb girdle weakness in advanced stages
• At some stage, occurrence of typical sharp shooting "lightning" pains lasting seconds to minutes
• Sensorineural hearing loss (variably present)
• Family history consistent with autosomal dominant inheritance

Treatment

Management of hereditary sensory neuropathy type 1 generally follows the guidelines for diabetic foot care, including careful cleansing and protection of wounds and surgical care when needed. Pain medications may be used by those who experience shooting pains. Clean and protect wounds on neuropathic limbs; surgical treatment similar to that for leprosy; ankle/foot orthotics for foot drop; arthrodesis for Charcot joints; pregabalin, carbamazepine, gabapentin, or amitryptiline, or a combination of an antiepileptic drug and an antidepressant drug for shooting pains. [1].

NIH genetic and rare disease info

• NIH info on Hereditary sensory neuropathy type 1

Hereditary sensory neuropathy type 1 is a rare disease.

Hereditary sensory neuropathy type 1 Resources
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