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Hereditary Sensory Neuropathy Type IA

Synonyms: HSAN1A, HSN1A, Hereditary Sensory and Autonomic Neuropathy Type IA
, MB BS, PhD
Department of Medicine
University of Sydney
Hereditary Neuropathies Clinic and Molecular Medicine Laboratory
Concord Hospital
Sidney, Australia

Initial Posting: ; Last Update: September 10, 2015.


Clinical characteristics.

Hereditary sensory neuropathy type IA (HSN1A) is an axonal form of hereditary motor and sensory neuropathy distinguished by prominent early sensory loss and later positive sensory phenomena including dysesthesia and characteristic "lightning" or "shooting" pains. Loss of sensation can lead to painless injuries, which, if unrecognized, result in slow wound healing and subsequent osteomyelitis requiring distal amputations. HSN1A is often associated with progressive sensorineural deafness. Motor involvement is present in all advanced cases and can be severe. After age 20 years, the distal wasting and weakness may involve proximal muscles so that a person in his/her 60s or 70s may require a wheelchair for mobility. Drenching sweating of the hands and feet is sometimes reported and occasionally pupillary abnormalities are observed; however, visceral signs of autonomic involvement are rare.


The clinical diagnosis of HSN1A is based on the presence of prominent sensory loss with foot ulcers and shooting pains in one or more affected members of a family with what appears to be a CMT2 syndrome (i.e., axonal form of hereditary motor and sensory neuropathy). The diagnosis is established by identification of a heterozygous pathogenic variant in SPTLC1.


Treatment of manifestations: Clean and protect wounds on neuropathic limbs; surgical treatment similar to that for leprosy; arthrodesis for Charcot joints; ankle/foot orthotics (AFOs) for foot drop; carbamazepine, gabapentin, or amitryptiline, or a combination of an antiepileptic drug and an antidepressant drug for shooting pains.

Prevention of secondary complications: Routine care by a diabetic foot care specialist to prevent/treat calluses and foot ulcers; education about good skin care and burn prevention (e.g., to hands when cooking).

Surveillance: At least daily inspection of feet for injuries or sources of wear.

Agents/circumstances to avoid: Opiates as they are addicting and HSN1A is a chronic disorder.

Other: Tendon transposition surgery is not likely to be useful as weakness of the posterior lower leg muscles may occur.

Genetic counseling.

HSN1A is inherited in an autosomal dominant manner. Most probands have an affected parent. Offspring of an affected individual have a 50% chance of inheriting the SPTLC1 pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant has been identified in the family.


No formal diagnostic criteria have been published.

Suggestive Findings

Hereditary sensory neuropathy type IA (HSN1A) 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 “lightening” pains lasting seconds to minutes
  • Sensorineural hearing loss (variably present)
  • Family history consistent with autosomal dominant inheritance

Establishing the Diagnosis

The diagnosis of HSN1A is established in a proband with suggestive clinical findings and identification of a heterozygous pathogenic variant in SPTLC1 on molecular genetic testing (see Table 1).

Molecular testing approaches can include single-gene testing, use of a multi-gene panel, and more comprehensive genomic testing.

  • Single-gene testing. Molecular genetic testing of SPTLC1 may begin with sequence analysis of exons 5 and 6. If no pathogenic variant is identified, further sequence analysis of SPTLC1 may be considered. However, only gain-of-function pathogenic variants affecting the SPT active site and the SPTLC2 subunit of the SPT dimer cause the phenotype. Note: No duplications or deletions have been found or are expected given the disease mechanism.
  • A multi-gene panel that includes SPTLC1 and other genes of interest (see Differential Diagnosis) may also be considered. Note: The genes included and sensitivity of multi-gene panels vary by laboratory and over time.
  • More comprehensive genomic testing (when available) including exome sequencing, genome sequencing, and mitochondrial sequencing may be considered if single-gene testing (and/or use of a multi-gene panel) fails to confirm a diagnosis in an individual with features of HSN1A. For more information on comprehensive genome sequencing click here.

Table 1.

Summary of Molecular Genetic Testing Used in Hereditary Sensory Neuropathy Type IA

Gene 1Test MethodProportion of Probands with a Pathogenic Variant 2 Detectable by This Method 3
Positive family historyNegative family history
SPTLC1Sequence analysis 4 of select exons 57 families (86%)N/A
Sequence analysis 4, 6N/A10 families (10%)
Gene-targeted deletion/duplication analysis 7NA 8

See Molecular Genetics for information on allelic variants detected in this gene.


Houlden et al [2006]; Author, personal communication


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Sequence variants in exon 5 (including p.Cys133Tyr and p.Cys133Trp) and exon 6 (p.Val144Asp) [Bejaoui et al 2001, Dawkins et al 2001]


Sequence variants including the known pathogenic variants p.Cys133Tyr, p.Cys133Trp, and p.Val144Asp


Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used can include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.


No duplications or deletions have been found or are expected as the disease mechanism involves a gain-of-function pathogenic variant of the active site of the enzyme.

Clinical Characteristics

Clinical Description

Hereditary sensory neuropathy type IA (HSN1A) is usually first noticed when painless injuries appear. Onset ranges from the teens to the sixth decade. Later, positive sensory phenomena occur (numbness, paresthesia, burning, and shooting pains). Shooting pains may be a distinctive but variable feature of HSN1.

If the sensory loss is unheeded, chronic ulcerations of the extremities may lead to osteomyelitis and require amputations. Neuropathic joints are common.

Weakness commences in the distal lower limbs, followed by the distal upper limbs and in severe cases, proximal upper- and lower-limb girdle muscles. Distal muscle weakness and wasting are present in all advanced cases. The weakness of ankle flexors produces a floppy, flipper-like foot rather than pes cavus.

A few instances of early severe motor involvement have been reported [Houlden et al 2006].

Older affected individuals may require wheelchairs for mobility.

Retained and even brisk proximal reflexes in some affected individuals may indicate some upper motor neuron involvement. Corticospinal degeneration was not observed in an autopsied case with a known SPTLC1 pathogenic variant, but data are limited.

Sensorineural hearing loss is variable. When present, its onset is in middle to late adulthood.

Rarely, pupillary abnormalities termed "tonic pupils" or pseudo-Argyll-Robertson pupils (i.e., those not associated with syphilis) are present.

Visceral autonomic features are rare [Nicholson, unpublished data], with abdominal pain, diarrhea, and weight loss reported in some individuals in one family only [Houlden et al 2006].

Electrophysiology is initially normal and is not useful for early detection [Author, personal observation].

  • Sensory nerve action potentials are reduced only late in the disease.
  • Motor nerve conduction velocities are normal until motor action potential amplitudes become reduced.
  • Motor nerve conduction velocities are mildly slowed and motor action potentials are reduced in advanced cases.

Sural nerve biopsy shows axonal degeneration with loss of both small and large fibers. These findings are nonspecific and not diagnostic.


The disease process affects the axons and cell bodies of dorsal root ganglia neurons and motor neurons in the anterior horns of the spinal cord. Studies show a distal axonal degeneration with loss of unmyelinated, small myelinated, and large myelinated fibers with decreasing severity in that order, proceeding to ganglion cell loss [Houlden et al 2006]. See review in Thomas [1993].


Variable penetrance has been observed [Houlden et al 2006].


An earlier age of onset in younger generations was noted in one study [Houlden et al 2006]; however, this could have been due to better recognition of the phenotype as earlier age of onset in younger generations has not been reported in any other publication.


The clinical classification of HSN1 has always been confusing. The term hereditary sensory neuropathy (HSN) was first used by Hicks [1922] to describe a family with associated spontaneous shooting pains and deafness. The family was later reported as having a form of peroneal muscular atrophy.

Motor involvement was also noted in other families in southern England and described by Ellison in his University of Edinburgh MD thesis, and later by Campbell & Hoffman [1964]. The Australian families with an SPTLC1 pathogenic variant described in the original linkage and mutation reports [Dawkins et al 2001] have no visceral autonomic symptoms and signs and share a common ancestor with the southern English families described by Ellison and reported by Campbell & Hoffman [1964] as having HSN. Therefore, the term HSN has been used here as in the review by Thomas [1993] and as listed in OMIM. Rarely, individuals with HSN1 have autonomic pupillary and bladder signs; thus, this disorder has been classified as a hereditary sensory and autonomic neuropathy (HSAN).

The term HSN is also less than ideal, as the disorder is a sensory and motor neuropathy. Therefore, strictly, it is a form of Charcot-Marie-Tooth neuropathy. The clinical appearance is that of a slowly progressive length-dependent adult-onset axonal form of Charcot-Marie-Tooth neuropathy (CMT type II, hereditary motor and sensory neuropathy, HMSN II) with dense sensory loss.

The term HSN1 designates dominantly inherited forms of hereditary sensory neuropathy. HSAN types 2 to 6 are recessively inherited forms of sensory and autonomic neuropathies.


An absolute figure cannot be given, but HSN affects 25 of 600 families (4.2%) with CMT studied by the author. Of these families with HSN, only 25% have HSN1A (1% of all families with CMT).

If the overall incidence of motor and sensory neuropathies is 30:100,000, the prevalence of HSN is on the order of 2:1,000,000. HSN1A may be underestimated because diagnosis previously depended erroneously on finding pure sensory involvement, shooting pains, and/or skin damage or ulcers.

Differential Diagnosis

Dominant forms of hereditary sensory neuropathy (HSN) are genetically heterogeneous:

Disorders with similar phenotypes are two forms of CMT2:

  • CMT2B, a motor and sensory neuropathy with severe sensory loss and foot ulcers but no shooting pains, described by Kwon et al [1995]. CMT2B is caused by mutation of RAB7 [Verhoeven et al 2003].
  • CMT2I/J. The MPZ p.Thr124Met pathogenic variant is associated with a phenotype almost identical to HSN1A, with severe sensory loss, shooting pains, and occasional pseudo Argyl-Robertson pupils but no ulcerations [De Jonghe et al 1999].

Painful diabetic neuropathy may have a similar phenotype but usually lacks a family history of neuropathy.

See Hereditary sensory and autonomic neuropathy: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.


Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with hereditary sensory neuropathy type IA, the following assessments are recommended:

  • Feet, ankles, and hands re the condition of the skin
  • Joints for evidence of Charcot joints
  • Strength
  • Loss of sweating and compensatory patchy hyperhydrosis
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Wounds on neuropathic limbs heal if they are clean and protected and the limb is rested. Principles of treatment are the same as for leprosy surgery; see Warren & Nade [1999].

Foot drop can be treated with ankle/foot orthotics (AFOs), but these need sleeving with stockings or some form of second skin to prevent skin abrasion.

Charcot joints may require arthrodesis.

Shooting pains are difficult to treat and only partial relief can be obtained with carbamazepine, gabapentin, or amitryptiline, or a combination of an antiepileptic and an antidepressant. Opiates are contraindicated as HSN1A is a chronic disorder.

Prevention of Secondary Complications

Foot ulcers are frequently caused by breakdown of callus. Therefore, it is important to prevent callus formation by removing sources of pressure and to treat existing callus by softening the skin. Routine foot care by a diabetic clinic or by a podiatrist instructed to treat as for a diabetic foot is recommended.

Burns can be prevented by using gloves as needed (e.g., during cooking).

A diabetic education clinic is an excellent source of advice regarding skin care.


Feet should be inspected at least daily for injuries or sources of wear.

Agents/Circumstances to Avoid

Opiates are contraindicated as this is a chronic disorder.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Penno et al [2010] found that HSN1A-causing pathogenic variants in SPTLC1 result in decreased specificity of the active site of the enzyme, allowing alanine and glycine into the active site and producing neurotoxic sphingoid bases. The finding suggests that HSN1A is caused by these toxic products and opens an avenue for possible (at present, experimental) therapeutic approaches. Addition of serine to the diet of an HSN1 animal model and to 14 humans with HSN1 was effective in reducing plasma levels of the toxic deoxysphingolipids [Garofalo et al 2011].

Search for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Hereditary sensory neuropathy type IA (HSN1A) is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

  • Most individuals diagnosed with HSN1A have an affected parent.
  • A proband with HSN1A may have the disorder as the result of a de novo SPTLC1 pathogenic variant. One apparent de novo pathogenic variant has been reported [Verhoeven et al 2004]; the proportion of HSN1A caused by a de novo pathogenic variant is unknown.
  • If the pathogenic variant found in the proband cannot be detected in leukocyte DNA of either parent, two possible explanations are germline mosaicism in a parent or a de novo pathogenic variant in the proband. Although no instances of germline mosaicism have been reported, it remains a possibility.
  • Although recommendations for evaluation of the parents of a proband with an apparent de novo pathogenic variant include clinical examination and electrophysiologic testing, diagnostic clinical and electrophysiologic findings have not been reported to emerge after age 30 years.
  • The family history of some individuals diagnosed with HSN1A may appear to be negative because of failure to recognize the disorder in family members, reduced penetrance, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent. Therefore, an apparently negative family history cannot be confirmed unless appropriate clinical evaluation and/or molecular genetic testing have been performed on the parents of the proband.

Sibs of a proband

  • The risk to each sib of the proband depends on the genetic status of the proband's parents.
  • If a parent of the proband is affected, the risk to each sib is 50%.
  • If the parents of a proband are clinically unaffected, sibs who are younger than age 30 years are still at increased risk for HSN1A because of the possibility of reduced penetrance in a parent.
  • If the SPTLC1 pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the risk to sibs is low but greater than that of the general population because of the possibility of germline mosaicism. Germline mosaicism has not been reported to date.

Offspring of a proband. Each child of an affected individual has a 50% chance of inheriting the SPTLC1 pathogenic variant.

Other family members. The risk to other family members depends on the status of the proband's parents: if a parent is affected, his or her family members are at risk.

Related Genetic Counseling Issues

Testing of at-risk asymptomatic adult relatives of individuals with HSN1A is possible after molecular genetic testing has identified the specific pathogenic variant in the family. Such testing should be performed in the context of formal genetic counseling, and is not useful in predicting age of onset, severity, type of symptoms, or rate of progression in asymptomatic individuals. Testing of asymptomatic at-risk individuals with nonspecific or equivocal symptoms is predictive testing, not diagnostic testing.

Testing of asymptomatic individuals younger than age 18 years who are at risk for adult-onset disorders for which no treatment exists is not considered appropriate, primarily because it negates the autonomy of the child with no compelling benefit. Further, concern exists regarding the potential unhealthy adverse effects that such information may have on family dynamics, the risk of discrimination and stigmatization in the future, and the anxiety that such information may cause.

If a diagnosis of HSN1A has been established in the family, it is appropriate to consider testing of symptomatic individuals regardless of age.

For more information, see the National Society of Genetic Counselors position statement on genetic testing of minors for adult-onset conditions and the American Academy of Pediatrics and American College of Medical Genetics and Genomics policy statement: ethical and policy issues in genetic testing and screening of children.

Considerations in families with an apparent de novo pathogenic variant. When neither parent of a proband with HSN1A has the SPTLC1 pathogenic variant or clinical evidence of the disorder, the pathogenic variant is likely de novo. However, other possible non-medical explanations that could also be explored include alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the SPTLC1 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for HSN1A are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although most centers would consider decisions about prenatal testing to be the choice of the parents, discussion of these issues is appropriate.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Hereditary Sensory Neuropathy Type IA: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus, locus name, critical region, complementation group from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B.

OMIM Entries for Hereditary Sensory Neuropathy Type IA (View All in OMIM)


Molecular Genetic Pathogenesis

Gene structure. The SPTLC1 reference sequence NM_006415.3 is the longest transcript variant and has 15 exons. For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. The following three pathogenic variants result in significant amino acid changes likely to have functional or structural effects.

Variant of uncertain significance. A p.Gly387Ala (rs119482084; OMIM 605712) variant was identified in two sisters of Belgian origin [Verhoeven et al 2004]; their parents were not available for testing. Since this change has been observed in the general population and in the homozygous state in a parent of an affected person [Hornemann et al 2009], it is unlikely to be pathogenic.

Table 2.

Selected SPTLC1 Pathogenic Variants

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences

Note on variant classification: Variants listed in the table have been provided by the author. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (www​ See Quick Reference for an explanation of nomenclature.

Normal gene product. The serine palmitoyltransferase light chain 1 has 473 amino acids.

Abnormal gene product. Pathogenic variants in the active sites of the SPTLC1 and SPTLC2 subunits result in a gain-of-function by altering substrate specificity allowing alanine and glycine to be incorporated into new toxic sphingolipids which cannot be degraded, leading to the accumulation of the toxic lipids 1-deoxy-sphinganine and 1-deoxymethyl-sphinganine. Raised levels of toxic deoxy-sphingoid bases (DSBs) 1-deoxy-sphinganine and 1-deoxymethyl-sphinganine have recently been reported in HSN1A plasma [Penno et al 2010].

Expression of the mutated gene product has not been investigated.

Overexpression of the wild type allele in a mouse model of HSN1A has reversed the phenotype [Eichler et al 2009]. This finding opens the prospect of possible treatments aimed at reducing the levels of these metabolites.


Published Guidelines/Consensus Statements

  • Committee on Bioethics; Committee on Genetics, and American College of Medical Genetics and Genomics: Social, Ethical, Legal Issues Committee. Ethical and policy issues in genetic testing and screening of children. Available online. Accessed 2-21-17. [PubMed: 23428972]
  • National Society of Genetic Counselors. Position statement on genetic testing of minors for adult-onset disorders. Available online. 2012. Accessed 2-21-17.

Literature Cited

  • Auer-Grumbach M, De Jonghe P, Verhoeven K, Timmerman V, Wagner K, Hartung HP, Nicholson GA. Autosomal dominant inherited neuropathies with prominent sensory loss and mutilations: a review. Arch Neurol. 2003;60:329–34. [PubMed: 12633143]
  • Auer-Grumbach M, Wagner K, Timmerman V, De Jonghe P, Hartung HP. Ulcero-mutilating neuropathy in an Austrian kinship without linkage to hereditary motor and sensory neuropathy IIB and hereditary sensory neuropathy I loci. Neurology. 2000;54:45–52. [PubMed: 10636124]
  • Bejaoui K, Wu C, Scheffler MD, Haan G, Ashby P, Wu L, de Jong P, Brown RH Jr. SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat Genet. 2001;27:261–2. [PubMed: 11242106]
  • Bellone E, Rodolico C, Toscano A, Di Maria E, Cassandrini D, Pizzuti A, Pigullo S, Mazzeo A, Macaione V, Girlanda P, Vita G, Ajmar F, Mandich P. A family with autosomal dominant mutilating neuropathy not linked to either Charcot-Marie-Tooth disease type 2B (CMT2B) or hereditary sensory neuropathy type I (HSN I) loci. Neuromuscul Disord. 2002;12:286–91. [PubMed: 11801401]
  • Campbell AM, Hoffman HL. Sensory radicular neuropathy associated with muscle wasting in two cases. Brain. 1964;87:67–74. [PubMed: 14152213]
  • Dawkins JL, Hulme DJ, Brahmbhatt SB, Auer-Grumbach M, Nicholson GA. Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet. 2001;27:309–12. [PubMed: 11242114]
  • De Jonghe P, Timmerman V, Ceuterick C, Nelis E, De Vriendt E, Lofgren A, Vercruyssen A, Verellen C, Van Maldergem L, Martin JJ, Van Broeckhoven C. The Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene is associated with a clinically distinct Charcot-Marie-Tooth phenotype. Brain. 1999;122:281–90. [PubMed: 10071056]
  • Eichler FS, Hornemann T, McCampbell A, Kuljis D, Penno A, Vardeh D, Tamrazian E, Garofalo K, Lee HJ, Kini L, Selig M, Frosch M, Gable K, von Eckardstein A, Woolf CJ, Guan G, Harmon JM, Dunn TM, Brown RH Jr. Overexpression of the wild-type SPT1 subunit lowers desoxysphingolipid levels and rescues the phenotype of HSAN1. J Neurosci. 2009;29:14646–51. [PMC free article: PMC3849752] [PubMed: 19923297]
  • Garofalo K, Penno A, Schmidt BP, Lee HJ, Frosch MP, von Eckardstein A, Brown RH, Hornemann T, Eichler FS. Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. J Clin Invest. 2011;121:4735–45. [PMC free article: PMC3225995] [PubMed: 22045570]
  • Hicks EP. Hereditary perforating ulcer of the foot. Lancet. 1922;1:319–21.
  • Hornemann T, Penno A, Richard S, Nicholson G, van Dijk FS, Rotthier A, Timmerman V, von Eckardstein A. A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated. Neurogenetics. 2009;10:135–43. [PubMed: 19132419]
  • Houlden H, King R, Blake J, Groves M, Love S, Woodward C, Hammans S, Nicoll J, Lennox G, O'Donovan DG, Gabriel C, Thomas PK, Reilly MM. Clinical, pathological and genetic characterization of hereditary sensory and autonomic neuropathy type 1 (HSAN I). Brain. 2006;129:411–25. [PubMed: 16364956]
  • Klein CJ, Botuyan MV, Wu Y, Ward CJ, Nicholson GA, Hammans S, Hojo K, Yamanishi H, Karpf AR, Wallace DC, Simon M, Lander C, Boardman LA, Cunningham JM, Smith GE, Litchy WJ, Boes B, Atkinson EJ, Middha S, Dyck PJ, Parisi JE, Mer G, Smith DI, Dyck PJ. Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet. 2011;43:595–600. [PMC free article: PMC3102765] [PubMed: 21532572]
  • Kok C, Kennerson ML, Spring PJ, Ing AJ, Pollard JD, Nicholson GA. A locus for hereditary sensory neuropathy with cough and gastroesophageal reflux on chromosome 3p22-p24. Am J Hum Genet. 2003;73:632–7. [PMC free article: PMC1180687] [PubMed: 12870133]
  • Kwon JM, Elliott JL, Yee WC, Ivanovich J, Scavarda NJ, Moolsintong PJ, Goodfellow PJ. Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q. Am J Hum Genet. 1995;57:853–8. [PMC free article: PMC1801519] [PubMed: 7573046]
  • Penno A, Reilly MM, Houlden H, Laurá M, Rentsch K, Niederkofler V, Stoeckli ET, Nicholson G, Eichler F, Brown RH Jr, von Eckardstein A, Hornemann T. Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids. J Biol Chem. 2010;285:11178–87. [PMC free article: PMC2856995] [PubMed: 20097765]
  • Thomas PK. Hereditary sensory neuropathies. Brain Pathol. 1993;3:157–63. [PubMed: 8293177]
  • Verhoeven K, Coen K, De Vriendt E, Jacobs A, Van Gerwen V, Smouts I, Pou-Serradell A, Martin JJ, Timmerman V, De Jonghe P. SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I. Neurology. 2004;62:1001–2. [PubMed: 15037712]
  • Verhoeven K, De Jonghe P, Coen K, Verpoorten N, Auer-Grumbach M, Kwon JM, FitzPatrick D, Schmedding E, De Vriendt E, Jacobs A, Van Gerwen V, Wagner K, Hartung HP, Timmerman V. Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy. Am J Hum Genet. 2003;72:722–7. [PMC free article: PMC1180247] [PubMed: 12545426]
  • Warren G, Nade S. The Care of Neuropathic Limbs: A Practical Manual. London and New York: Parthenon Publishing; 1999.

Suggested Reading

Chapter Notes

Revision History

  • 10 September 2015 (me) Comprehensive update posted live
  • 7 March 2013 (me) Comprehensive update posted live
  • 3 May 2012 (gn) Revision: edits to Therapies Under Investigation
  • 15 March 2012 (cd) Revision: targeted mutation analysis no longer listed as available clinically in the GeneTests™ Laboratory Directory
  • 22 September 2011 (cd) Revision: addition to Differential Diagnosis; change in disease nomenclature (HSN1 → HSN1A)
  • 20 July 2010 (me) Comprehensive update posted live
  • 2 October 2007 (me) Comprehensive update posted to live Web site
  • 11 March 2005 (me) Comprehensive update posted to live Web site
  • 28 September 2004 (me) Comprehensive update posted to live Web site
  • 21 May 2004 (gn) Revision: prenatal testing available
  • 23 September 2002 (me) Review posted to live Web site
  • 21 March 2002 (gn) Original submission
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