Full Report

Format

Full Report
Summary (Text)
Summary (XML)

Send to:

Choose Destination

File
Clipboard
Collections

Image

details

Congenital insensitivity to pain-hypohidrosis syndrome(HSAN8)

MedGen UID:: 894363
•Concept ID:: C4225308
•: Disease or Syndrome

Synonyms:	HSAN VIII; Neuropathy, hereditary sensory and autonomic, type VIII
SNOMED CT:	HSAN8 - hereditary sensory and autonomic neuropathy type 8 (1172838005); Hereditary sensory and autonomic neuropathy type 8 (1172838005); Hereditary sensory and autonomic neuropathy type VIII (1172838005)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	PRDM12 (9q34.12)

Monarch Initiative:	MONDO:0014662
OMIM®:	616488
Orphanet:	ORPHA478664

Definition

Hereditary sensory and autonomic neuropathy type VIII (HSAN8) is an autosomal recessive neurologic disorder characterized by congenital insensitivity to pain resulting in ulceration to the fingers, tongue, lips, and other distal appendages. Affected individuals may also have decreased sweating and tear production (summary by Chen et al., 2015). For a discussion of genetic heterogeneity of hereditary sensory and autonomic neuropathy, see HSAN1A (162400). [from OMIM]

Clinical features

From HPO

Gastrointestinal dysmotility

MedGen UID:: 324638
•Concept ID:: C1836923
•: Finding

Abnormal intestinal contractions, such as spasms and intestinal paralysis, related to the loss of the ability of the gut to coordinate muscular activity because of endogenous or exogenous causes.

See: Feature record | Search on this feature

Sensorineural hearing loss disorder

MedGen UID:: 9164
•Concept ID:: C0018784
•: Disease or Syndrome

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

See: Feature record | Search on this feature

Hypoesthesia

MedGen UID:: 6974
•Concept ID:: C0020580
•: Finding

Decreased ability to perceive touch.

See: Feature record | Search on this feature

Pain insensitivity

MedGen UID:: 488855
•Concept ID:: C0344307
•: Finding

Inability to perceive painful stimuli.

See: Feature record | Search on this feature

Hyporeflexia

MedGen UID:: 195967
•Concept ID:: C0700078
•: Finding

Reduction of neurologic reflexes such as the knee-jerk reaction.

See: Feature record | Search on this feature

Impaired vibratory sensation

MedGen UID:: 220959
•Concept ID:: C1295585
•: Finding

A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient.

See: Feature record | Search on this feature

Impaired proprioception

MedGen UID:: 346424
•Concept ID:: C1856691
•: Finding

A loss or impairment of the sensation of the relative position of parts of the body and joint position.

See: Feature record | Search on this feature

Hyposmia

MedGen UID:: 473584
•Concept ID:: C2364082
•: Finding

A decreased sensitivity to odorants (that is, a decreased ability to perceive odors).

See: Feature record | Search on this feature

Intellectual disability

MedGen UID:: 811461
•Concept ID:: C3714756
•: Mental or Behavioral Dysfunction

Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

See: Feature record | Search on this feature

Impaired temperature sensation

MedGen UID:: 866867
•Concept ID:: C4021222
•: Finding

A reduced ability to discriminate between different temperatures.

See: Feature record | Search on this feature

Corneal scarring

MedGen UID:: 83899
•Concept ID:: C0349702
•: Finding

Replacement of corneal tissue with scar tissue as a result of injury to the deeper layers of the cornea.

See: Feature record | Search on this feature

Recurrent skin infections

MedGen UID:: 377848
•Concept ID:: C1853193
•: Disease or Syndrome

Infections of the skin that happen multiple times.

See: Feature record | Search on this feature

Hypohidrosis

MedGen UID:: 43796
•Concept ID:: C0020620
•: Disease or Syndrome

Abnormally diminished capacity to sweat.

See: Feature record | Search on this feature

Corneal ulceration

MedGen UID:: 40486
•Concept ID:: C0010043
•: Disease or Syndrome

Disruption of the epithelial layer of the cornea with involvement of the underlying stroma.

See: Feature record | Search on this feature

Decreased lacrimation

MedGen UID:: 116004
•Concept ID:: C0235857
•: Finding

Abnormally decreased lacrimation, that is, reduced ability to produce tears.

See: Feature record | Search on this feature

Show all Hide all

Abnormality of the digestive system
- Gastrointestinal dysmotility
Abnormality of the eye
- Corneal ulceration
- Decreased lacrimation
Abnormality of the immune system
- Recurrent skin infections
Abnormality of the integument
- Hypohidrosis
Abnormality of the musculoskeletal system
- Corneal scarring
Abnormality of the nervous system
Ear malformation
- Sensorineural hearing loss disorder

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVCongenital insensitivity to pain-hypohidrosis syndrome

Autosomal recessive hereditary sensory and autonomic neuropathy
- Congenital insensitivity to pain-hypohidrosis syndrome

Professional guidelines

PubMed

Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline.

Nordenström A, Ahmed SF, van den Akker E, Blair J, Bonomi M, Brachet C, Broersen LHA, Claahsen-van der Grinten HL, Dessens AB, Gawlik A, Gravholt CH, Juul A, Krausz C, Raivio T, Smyth A, Touraine P, Vitali D, Dekkers OM
Eur J Endocrinol 2022 Apr 21;186(6):G9-G49. doi: 10.1530/EJE-22-0073. PMID: 35353710 Free PMC Article

Clinical management in mixed gonadal dysgenesis with chromosomal mosaicism: Considerations in newborns and adolescents.

Weidler EM, Pearson M, van Leeuwen K, Garvey E
Semin Pediatr Surg 2019 Oct;28(5):150841. Epub 2019 Sep 19 doi: 10.1016/j.sempedsurg.2019.150841. PMID: 31668295 Free PMC Article

Treatment of congenital malformations.

Brucker SY, Rall K, Campo R, Oppelt P, Isaacson K
Semin Reprod Med 2011 Mar;29(2):101-12. Epub 2011 Mar 24 doi: 10.1055/s-0031-1272472. PMID: 21437824

See all (26)

Recent clinical studies

Etiology

Challenges Waiting for an Adult with DSD.

Nowotny HF, Reisch N
Horm Res Paediatr 2023;96(2):207-221. Epub 2022 Dec 6 doi: 10.1159/000527433. PMID: 36473446

Painful and painless channelopathies.

Bennett DL, Woods CG
Lancet Neurol 2014 Jun;13(6):587-99. Epub 2014 May 6 doi: 10.1016/S1474-4422(14)70024-9. PMID: 24813307

Management of vaginal agenesis.

Nakhal RS, Creighton SM
J Pediatr Adolesc Gynecol 2012 Dec;25(6):352-7. Epub 2011 Aug 27 doi: 10.1016/j.jpag.2011.06.003. PMID: 21872517

Congenital corneal anesthesia.

Ramaesh K, Stokes J, Henry E, Dutton GN, Dhillon B
Surv Ophthalmol 2007 Jan-Feb;52(1):50-60. doi: 10.1016/j.survophthal.2006.10.004. PMID: 17212990

Inherited autonomic neuropathies.

Axelrod FB, Hilz MJ
Semin Neurol 2003 Dec;23(4):381-90. doi: 10.1055/s-2004-817722. PMID: 15088259

See all (133)

Diagnosis

The role of steroid hormones in the sexual differentiation of the human brain.

Bakker J
J Neuroendocrinol 2022 Feb;34(2):e13050. Epub 2021 Oct 27 doi: 10.1111/jne.13050. PMID: 34708466

Gender identity disorder (GID) in adolescents and adults with differences of sex development (DSD): A systematic review and meta-analysis.

Babu R, Shah U
J Pediatr Urol 2021 Feb;17(1):39-47. Epub 2020 Nov 12 doi: 10.1016/j.jpurol.2020.11.017. PMID: 33246831

Painful and painless channelopathies.

Bennett DL, Woods CG
Lancet Neurol 2014 Jun;13(6):587-99. Epub 2014 May 6 doi: 10.1016/S1474-4422(14)70024-9. PMID: 24813307

Congenital corneal anesthesia.

Ramaesh K, Stokes J, Henry E, Dutton GN, Dhillon B
Surv Ophthalmol 2007 Jan-Feb;52(1):50-60. doi: 10.1016/j.survophthal.2006.10.004. PMID: 17212990

Inherited autonomic neuropathies.

Axelrod FB, Hilz MJ
Semin Neurol 2003 Dec;23(4):381-90. doi: 10.1055/s-2004-817722. PMID: 15088259

See all (198)

Therapy

Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline.

Sodium Channels in Human Pain Disorders: Genetics and Pharmacogenomics.

Dib-Hajj SD, Waxman SG
Annu Rev Neurosci 2019 Jul 8;42:87-106. Epub 2019 Jan 31 doi: 10.1146/annurev-neuro-070918-050144. PMID: 30702961

Hormone-Based Treatments in Subfertile Males.

Patel DP, Chandrapal JC, Hotaling JM
Curr Urol Rep 2016 Aug;17(8):56. doi: 10.1007/s11934-016-0612-4. PMID: 27292256

Sodium channelopathies and pain.

Lampert A, O'Reilly AO, Reeh P, Leffler A
Pflugers Arch 2010 Jul;460(2):249-63. Epub 2010 Jan 26 doi: 10.1007/s00424-009-0779-3. PMID: 20101409

Amenorrhea.

Marchant DJ
Clin Obstet Gynecol 1969 Sep;12(3):693-707. doi: 10.1097/00003081-196909000-00010. PMID: 5388335

See all (51)

Prognosis

Congenital insensitivity to pain: a novel mutation affecting a U12-type intron causes multiple aberrant splicing of SCN9A.

Marchi M, D'Amato I, Andelic M, Cartelli D, Salvi E, Lombardi R, Gumus E, Lauria G
Pain 2022 Jul 1;163(7):e882-e887. Epub 2021 Nov 15 doi: 10.1097/j.pain.0000000000002535. PMID: 34799533 Free PMC Article

Rare Diseases Leading to Childhood Glaucoma: Epidemiology, Pathophysiogenesis, and Management.

Abdolrahimzadeh S, Fameli V, Mollo R, Contestabile MT, Perdicchi A, Recupero SM
Biomed Res Int 2015;2015:781294. Epub 2015 Sep 16 doi: 10.1155/2015/781294. PMID: 26451378 Free PMC Article

Consequences of chromsome18q deletions.

Cody JD, Sebold C, Heard P, Carter E, Soileau B, Hasi-Zogaj M, Hill A, Rupert D, Perry B, O'Donnell L, Gelfond J, Lancaster J, Fox PT, Hale DE
Am J Med Genet C Semin Med Genet 2015 Sep;169(3):265-80. Epub 2015 Aug 3 doi: 10.1002/ajmg.c.31446. PMID: 26235940

Congenital corneal anesthesia.

Ramaesh K, Stokes J, Henry E, Dutton GN, Dhillon B
Surv Ophthalmol 2007 Jan-Feb;52(1):50-60. doi: 10.1016/j.survophthal.2006.10.004. PMID: 17212990

Tissue glucocorticoid resistance/hypersensitivity syndromes.

Kino T, De Martino MU, Charmandari E, Mirani M, Chrousos GP
J Steroid Biochem Mol Biol 2003 Jun;85(2-5):457-67. doi: 10.1016/s0960-0760(03)00218-8. PMID: 12943736

See all (57)

Clinical prediction guides

Congenital insensitivity to pain: a novel mutation affecting a U12-type intron causes multiple aberrant splicing of SCN9A.

Congenital insensitivity to pain with anhidrosis syndrome: A series from Jordan.

Masri A, Shboul M, Khasawneh A, Jadallah R, ALmustafa A, Escande-Beillard N, Hamamy H, Bakri F, Reversade B
Clin Neurol Neurosurg 2020 Feb;189:105636. Epub 2019 Dec 9 doi: 10.1016/j.clineuro.2019.105636. PMID: 31841741

Atypical defects resulting in growth hormone insensitivity.

Wit JM, de Luca F
Growth Horm IGF Res 2016 Jun;28:57-61. Epub 2015 Nov 30 doi: 10.1016/j.ghir.2015.11.005. PMID: 26670721

A Cross-Section Study of the Ontogeny of Gender Roles in Women with DSD.

Wisniewski A, Aston CE
Curr Pediatr Rev 2015;11(1):27-35. doi: 10.2174/1573396311666150501003541. PMID: 25938375

Androgen insensitivity syndrome.

Mendoza N, Motos MA
Gynecol Endocrinol 2013 Jan;29(1):1-5. Epub 2012 Jul 20 doi: 10.3109/09513590.2012.705378. PMID: 22812659

See all (78)