Hereditary Sensory and Autonomic Neuropathy IV (HSAN IV)

Congenital insensitivity to pain with anhidrosis is a rare form of hereditary sensory and autonomic neuropathy. Characteristic features are indifference to painful stimuli, self-mutilating behavior, anhidrosis (inability to sweat), corneal ulcers, and sometimes hypogammaglobulinemia and recurrent infections, skin changes, osteomyelitis, bone fractures, and cognitive impairment. The patients' inability to sweat usually leads to recurrent episodes of unexplained fever and can be fatal due to hyperthermia, especially in infants and small children. The lack of pain sensation is thought to stem from the absence of the dorsal root ganglia responsible for pain sensation, while anhidrosis is due to the loss of innervation of eccrine sweat glands by sympathetic neurons.

Tests Available

Forms and Documents

Test Details

NTRK1
  • Confirmation of the clinical diagnosis
  • Carrier testing in unaffected family members
  • Prenatal diagnosis in families with an affected child and known mutation(s)
  • Capillary Sequencing

Ordering

239
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 705 Disorders of sweat glands
  • 778.4 Other disturbances of temperature regulation of newborn, Dehydration fever in newborn, Environmentally induced pyrexia, Hyperthermia in newborn, Transitory fever of newborn
  • 742.8 Other specified anomalies of nervous system, Agenesis of nerve, Displacement of brachial plexus, Familial dysautonomia, Jaw-winking syndrome, Marcus-Gunn syndrome, Riley-Day syndrome
* For price inquiries please email zebras@genedx.com

References

  1. Wieczorek S, et al. Neuromuscul Disord. 2008; 18:681-4
  2. Rotthier A, et al. Brain. 2009; 132:2699-711
  3. Indo Y, et al. Hum Mutat. 2001; 18:462-71
  4. Houlden H, et al. Neurol. 2001; 49:521-5
  5. Kilic S, et al. Neurogenetics. 2009; 10:161-5

Forms and Documents

Test Details

AARS, ATL1, ATP7A, BSCL2, DNAJB2, DNM2, DNMT1, DYNC1H1, EGR2, FAM134B, FGD4, FIG4, GAN, GARS, GDAP1, GJB1, GLA, HINT1, HSPB1, HSPB8, IGHMBP2, IKBKAP, INF2, KIF1A, KIF5A, LITAF, LMNA, LRSAM1, MFN2, MPZ, MTMR2, NDRG1, NEFL, NGF, NTRK1, PLEKHG5, PMP22, PRPS1, PRX, RAB7A, REEP1 (C2ORF23), SBF2, SCN9A, SH3TC2, SLC12A6, SLC52A2, SPTLC1, SPTLC2, TFG, TRPV4, TTR, WNK1, YARS
  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management of individuals with neuropathy
  • Testing of at-risk relatives for specific known mutation(s) previously identified in an affected family member
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

737
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81325x1, 81404x1, 81405x4, 81406x4
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Rotthier et al. (2012). Nat Rev Neurol 8: 73-85.
  2. McLaughlin et al. (2012) Hum Mutat 33(1): 244-253.
  3. Claeys et al. (2009) Brain 132:1741-1752.
  4. Harms et al. (2012) Neurol 78:1741-1720.
  5. Poirier et al. (2013) Nat Genet 45(6): 639.
  6. Bird (Updated March 2015). CharcotMarie-Tooth Neuropathy Type 1. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org
  7. Bird (Updated March 2015). CharcotMarie-Tooth Neuropathy Type 1. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org.
  8. Saporta et al. (2011) Ann Neurol 69(1): 22-33
  9. Siskind et al. (2013) J Genet Counsel 22: 422-436.
  10. Capponi et al. (2011) J Peripheral Nervous System 16: 287-294.
  11. Irobi et al. (2004) Hum Molec Genet 13(2): R195-R202.
  12. Bird (Updated April 2015). Charcot-Marie-Tooth Neuropathy Type 2. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org..
  13. Weterman et al. (2012) Hum Molec Genet 21(2): 358-370.
  14. Guernsey et al. (2010) PLoS Genetics 6(8): 1-7.
  15. Reilly et al. (2011) J Periph Nervous System 16: 1-14.
  16. Baets et al. (2011) Brain 134: 2664-2676.
  17. Vallat et al. (2013). Curr Opin Neurol 26(5): 473-480.
  18. Nelis et al. (2006) Eur J Hum Genet 4(1): 25-33
  19. Kim and Kim (Updated June 2013). Charcot-Marie-Tooth Neuropathy X Type 5 In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org.
  20. Davidson et al. (2012) J Neurol 259: 1673-1685.
  21. Azzedine, Bontoux, and LeGuern (Updated July 2010). Charcot-Marie-Tooth Neuropathy Type 4C. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http:/
  22. Moizard et al. (2010) Clin Genet 79(3): 243-253.
  23. Ito (Updated June 2012). BSCL2-Related Neurologic Disorders/Seipinopathy. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org
  24. Blumen et al. (2012) Ann Neurol 71: 509-519.
  25. Kuhlenbaumer G, Timmerman V, Bomont P (Updated June 2012). Giant Axonal Neuropathy. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.gen
  26. Mehta (Updated March 2011). Fabry Disease. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org.
  27. Guenther et al. (2007) Hum Mut 28(8): 808-815.
  28. Rossor et al. (2012) J Neurol Neurosurg Psychiatry 83: 6-14.
  29. Kim et al. (2013) Orphanet J Rare Dis 8:104
  30. Zuchner et al. (2006) Am J Hum Genet 79(2): 365- 369.
  31. Beetz et al. (2012) Am J Hum Genet 91: 139-145.
  32. Howard et al. (2002) Nat Genet 32: 384-392
  33. Ishiura et al. (2012) Am J Hum Genet 91: 320-329.
  34. Sekijima et al (Updated January 2012). Familial Transthyretin Amyloidosis. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.or
  35. Durr et al. (2004) Arch Neurol 61: 1867-1872
  36. Guelly et al. (2011) Am J Hum Genet 88:99-105
  37. Klein (Updated May 2012) DNMT1- Related Dementia, Deafness, and Sensory Neuropathy. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.gen
  38. Auer-Grumbach et al. (2006) NeuroMolecular Medicine 8: 147-159.
  39. Riviere et al. (2011). Am J Hum Genet 89: 219-230.
  40. Faber et al. (2012) Ann Neurol 71(1): 26-39.
  41. Rotthier et al. (2010) Am J Hum Genet 87: 513-522.
  42. Lo Giudice et al. (2014) Exp Neurol 25: 518-39.
  43. Horga et al. (2015) J. Neurol. 262 (8):1984-6 (PMID: 26194197)
  44. Foley et al. (2014) Brain : A Journal Of Neurology 137 (Pt 1):44-56 (PMID: 24253200)
  45. Boyer et al. (2011) The New England Journal Of Medicine 365 (25):2377-88 (PMID: 22187985)
  46. Goizet et al. (2009) Human Mutation 30 (2):E376-85 (PMID: 18853458)
  47. Jordanova et al. (2006) Nature Genetics 38 (2):197-202 (PMID: 16429158).