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Disease Profile

Hereditary sensory and autonomic neuropathy type 2

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

G60.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

HSAN2; Hereditary sensory neuropathy type 2; Hereditary sensory radicular neuropathy, recessive form;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 970

Definition
A rare hereditary sensory and autonomic neuropathy characterized by profound and universal sensory loss involving large and small fiber nerves.

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

Clinical description
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.

Etiology
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.

Diagnostic methods
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
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).

Genetic counseling
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 and treatment
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.

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

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal cortical bone morphology
0003103
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Abnormality of the ankles
0003028
Abnormality of the hip bone
Abnormality of the hips
0003272
Abnormality of the knee
0002815
Dystrophic fingernails
Poor fingernail formation
0008391
Dystrophic toenail
Poor toenail formation
0001810
Foot acroosteolysis
0001842
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Hyperlordosis
Prominent swayback
0003307
Reduced bone mineral density
Low solidness and mass of the bones
0004349
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
Tapered finger
Tapered fingertips
Tapering fingers

[ more ]

0001182
Wormian bones
Extra bones within cranial sutures
0002645
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

0001939
Acral ulceration
0006121
Anhidrosis
Lack of sweating
Sweating dysfunction

[ more ]

0000970
Areflexia
Absent tendon reflexes
0001284
Autoamputation of digits
0007460
Autosomal recessive inheritance
0000007
Decreased corneal reflex
0008000
Decreased nerve conduction velocity
0000762
Decreased number of peripheral myelinated nerve fibers
0003380
Decreased sensory nerve conduction velocity
0003448
Episodic hyperhidrosis
Sporadic excessive sweating
0001069
Feeding difficulties in infancy
0008872
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Hypogeusia
Decreased taste
Decreased taste sensation

[ more ]

0000224
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Muscular hypotonia
Low or weak muscle tone
0001252
Osteolytic defects of the phalanges of the hand
Breakdown of small bones of fingers
0009771
Painless fractures due to injury
0002661
Paronychia
0001818
Peripheral neuropathy
0009830
Slow progression
Signs and symptoms worsen slowly with time
0003677

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Hereditary sensory and autonomic neuropathy type 2. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Hereditary sensory and autonomic neuropathy type 2. Click on the link to view a sample search on this topic.