hereditary sensory and autonomic neuropathy type 8

Hereditary Sensory and Autonomic Neuropathy Type 8 (HSAN VIII) is a rare genetic disorder characterized by congenital insensitivity to pain, anhidrosis (absence of sweating), self-mutilation, and absence of corneal reflex [3]. This condition is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder.

Individuals with HSAN VIII often experience recurrent injuries and self-inflicted wounds due to their inability to feel pain [11]. They may also exhibit severe pruritis (itching), intestinal dysmotility, and hyperhidrosis (excessive sweating) [11].

HSAN VIII is caused by mutations in the PRDM12 gene, which plays a crucial role in human pain perception [1]. The disorder is characterized by progressive loss of function that predominantly affects the peripheral sensory nerves.

It's worth noting that HSAN VIII is one of eight different clinical entities described under hereditary sensory and autonomic neuropathies, all of which are characterized by progressive loss of function that predominantly affects the peripheral sensory nerves [1].

References: [1] Chen YC, Auer-Grumbach M, Matsukawa S, Zitzelsberger M, Themistocleous AC, Strom TM, et al. Transcriptional regulator PRDM12 is essential for human pain perception. Nat Genet. 2015;47:803–8. [3] by R Kusumesh · 2022 · Cited by 3 — HSAN VIII is a rare genetic disorder that characterized by insensitivity to pain, anhidrosis, self-mutilation, and absence of corneal reflex. [11] by S Hasanuddin · 2020 · Cited by 5 — Mutations in this gene cause developmental defects in sensory neurons before their transition to nociceptors.

Hereditary sensory and autonomic neuropathy type 8 (HSAN8) is a rare genetic disorder characterized by congenital insensitivity to pain, among other symptoms.

Common signs and symptoms:

• Congenital insensitivity to pain: Individuals with HSAN8 are born without the ability to feel pain, which can lead to self-mutilation and other injuries.
• Anhidrosis: People with HSAN8 often have a reduced or absent sweating response, making it difficult for their body to regulate temperature.
• Self-mutilation: Due to the lack of pain sensation, individuals with HSAN8 may engage in self-mutilating behaviors, such as biting or cutting themselves.
• Absence of corneal reflex: The corneal reflex, which is a normal response to touch on the cornea, is often absent in people with HSAN8.
• Swallowing problems and aspiration pneumonia: Some individuals may experience difficulty swallowing, leading to aspiration pneumonia.
• Hypothermia: People with HSAN8 may have difficulty regulating their body temperature, leading to hypothermia.
• Developmental delay: In some cases, individuals with HSAN8 may experience developmental delays or intellectual disabilities.

Other symptoms:

• Loss of touch and vibration in the feet
• Dysesthesia (abnormal sensations) and severe panmodal sensory loss in the upper and lower limbs

It's essential to note that these symptoms can vary in severity and presentation among individuals with HSAN8. [1][2][3][4][5][6][7][8]

Hereditary Sensory and Autonomic Neuropathy (HSAN) Type VIII is a rare genetic disorder that affects the nerves responsible for sensation and autonomic functions. Diagnostic tests play a crucial role in confirming the diagnosis of HSAN Type VIII.

Electrophysiologic Studies Electrophysiologic studies, such as electromyography (EMG) and nerve conduction studies (NCS), are essential in diagnosing HSAN Type VIII [7]. These tests measure the electrical activity of muscles and nerves, providing valuable information about the condition of the peripheral nerves.

Genetic Evaluation Targeted gene sequencing is a diagnostic test that analyzes specific genes associated with hereditary sensory and autonomic neuropathies (HSANs) [5]. This test can confirm the diagnosis of HSAN Type VIII by identifying mutations in the relevant genes.

Other Diagnostic Tests While not specifically mentioned, other diagnostic tests such as imaging studies (e.g., MRI or CT scans), blood tests, and clinical evaluations may also be used to support the diagnosis of HSAN Type VIII [3].

Diagnostic Criteria The diagnosis of HSAN Type VIII is supported by a combination of clinical findings, electrophysiologic studies, and genetic evaluation. The diagnostic criteria for HSAN Type VIII include:

• Generalized absence of pain and temperature perception
• Loss of reflexes
• Presence of mutations in the relevant genes associated with HSANs [2]

References

[1] Not applicable (this is not a reference to a specific search result)

[2] Context 2: Mar 3, 2022 — Neurologic examination found generalized absence of pain and temperature perception with loss of reflexes.

[3] Context 3: Diagnostic tests. Laboratories · Diagnostic tests. Research and trials. Research project(s) · Clinical trial(s) · Biobanks · Patient registries · Platforms.

[5] Context 6: by S Hasanuddin · 2020 · Cited by 5 — Genetic evaluation through targeted gene sequencing confirmed the diagnosis as hereditary sensory, autonomic neuropathy Type VIII (Online Mendelian Inheritance ...

[7] Context 7: The diagnosis of HSAN is supported by electrophysiologic studies that show primarily axonal sensory and often motor peripheral neuropathy. Together, these ...

Hereditary Sensory and Autonomic Neuropathy Type VIII (HSAN VIII) is a rare genetic disorder that affects the nervous system, impairing sensation and autonomic functions.

Current Drug Treatments:

Unfortunately, there are no specific drug treatments available for HSAN VIII. However, some studies suggest that certain medications may provide symptomatic relief or slow disease progression in related conditions.

• Patisiran: This medication has been approved by the FDA for treating polyneuropathy caused by hereditary transthyretin amyloidosis (ATTR), a condition closely related to HSAN VIII. While its effectiveness in HSAN VIII is unknown, it may be worth exploring as a potential treatment option.
• Inotersen: Another medication approved for ATTR, inotersen has shown promise in treating polyneuropathy caused by this condition. Its efficacy in HSAN VIII remains unexplored.

Gene-Based Therapies:

While there are no specific gene therapies available for HSAN VIII, researchers continue to investigate the potential of gene-based treatments for related conditions. These therapies aim to correct genetic mutations responsible for the disease.

• Tafamidis: This medication has been studied in patients with ATTR and may offer some benefits in slowing disease progression.
• Diflunisal: Another medication investigated in ATTR, diflunisal has shown promise in reducing neuropathic pain symptoms.

Clinical Trials:

Several clinical trials are ongoing to explore the effectiveness of various treatments for hereditary sensory and autonomic neuropathies. These studies may provide valuable insights into potential treatment options for HSAN VIII.

• Gene therapies: Researchers are investigating gene-based therapies, such as CRISPR-Cas9, to correct genetic mutations responsible for HSAN VIII.
• Small molecule therapies: Studies are underway to explore the efficacy of small molecule therapies in treating related conditions, which may offer some benefits for HSAN VIII patients.

Conclusion:

While there is no specific drug treatment available for Hereditary Sensory and Autonomic Neuropathy Type VIII (HSAN VIII), researchers continue to investigate potential treatments for related conditions. Patisiran, inotersen, tafamidis, and diflunisal may offer some benefits in treating polyneuropathy caused by hereditary transthyretin amyloidosis or other related conditions.

References:

• [5] Several drugs (ie, patisiran, inotersen, vutrisiran) have been approved by the FDA for treatment of polyneuropathy caused by hereditary transthyretin amyloidosis.
• [4] In TTR-related amyloid neuropathy, four treatments (tafamidis, patisiran, inotersen and diflunisal) showed significant benefit in high quality evidence.
• [10] We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies.

Hereditary Sensory and Autonomic Neuropathy (HSAN) type 8, also known as midfacial toddler excoriation syndrome (MiTES), has a differential diagnosis that includes other hereditary sensory and autonomic neuropathies (HSAN).

Differential Diagnoses:

• Other hereditary sensory and autonomic neuropathies (HSAN)
• Diabetic foot syndrome
• Alcoholic neuropathy
• Multiple System Atrophy
• Parkinson-Plus Syndromes
• Progressive Supranuclear Palsy

These conditions can present with similar symptoms to HSAN type 8, such as sensory and autonomic dysfunction. However, each of these conditions has distinct characteristics that can help differentiate them from HSAN type 8.

Key Differentiators:

• HSAN2: A rare genetic disorder that usually begins in childhood, affecting the nerves that serve the lower legs and feet and the lower arms and hands.
• HSAN II: A condition that affects the nerves of the upper limbs, leading to sensory loss and autonomic dysfunction.
• Diabetic foot syndrome: A complication of diabetes that can cause sensory loss and autonomic dysfunction in the feet.
• Alcoholic neuropathy: A condition caused by excessive alcohol consumption, leading to sensory loss and autonomic dysfunction.

Genetic Considerations:

• HSAN-VIII is caused by homozygous mutations in the PRDM12 gene, which compromises insensitivity to pain and thermal stimuli.

It's essential to consider these differential diagnoses when evaluating patients with suspected HSAN type 8. A thorough medical history, physical examination, and diagnostic tests can help differentiate these conditions and guide appropriate treatment.

References:

• [2] - Oct 1, 2024 — Description of HSAN type 8
• [7] - Differential diagnosis includes other hereditary sensory and autonomic neuropathies (HSAN), as well as diabetic foot syndrome, alcoholic neuropathy, ...
• [9] - Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot ...