U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Familial dysautonomia(HSAN3)

MedGen UID:
41678
Concept ID:
C0013364
Disease or Syndrome
Synonyms: FD; Hereditary sensory and autonomic neuropathy 3; Hereditary sensory neuropathy type 3; HSAN 3; HSAN III; HSAN3; HSN 3; NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE III; Riley Day syndrome
SNOMED CT: Hereditary sensory and autonomic neuropathy type III (29159009); HSAN III (29159009); Hereditary sensory and autonomic neuropathy, type III (29159009); Familial dysautonomia (29159009); Riley-Day syndrome (29159009); Dominant hereditary sensory neuropathy, type III (29159009)
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).
 
Gene (location): ELP1 (9q31.3)
 
Monarch Initiative: MONDO:0009131
OMIM®: 223900
Orphanet: ORPHA1764

Disease characteristics

Excerpted from the GeneReview: Familial Dysautonomia
Familial dysautonomia, which affects the development and survival of sensory, sympathetic, and parasympathetic neurons, is a debilitating disorder present from birth. Neuronal degeneration progresses throughout life. Affected individuals have gastrointestinal dysfunction, autonomic crises (i.e., hypertensive vomiting attacks), recurrent pneumonia, altered pain sensitivity, altered temperature perception, and blood pressure instability. Hypotonia contributes to delay in acquisition of motor milestones. Optic neuropathy results in progressive vision loss. Older individuals often have a broad-based and ataxic gait that deteriorates over time. Developmental delay / intellectual disability occur in about 21% of individuals. Life expectancy is decreased. [from GeneReviews]
Authors:
Bat-El Bar-Aluma   view full author information

Additional descriptions

From OMIM
Hereditary sensory and autonomic neuropathy type III (HSAN3) is an autosomal recessive neurodegenerative disorder with onset soon after birth. Affected individuals show progressive symptoms resulting from depletion of sensory proprioceptive and autonomic neurons. Features include gastrointestinal dysfunction, gastroesophageal reflux, vomiting crises, recurrent pneumonia, seizures, gait abnormalities with loss of ambulation, kyphoscoliosis, postural hypotension, hypertension crises, absence of fungiform papillae on the tongue, decreased deep tendon reflexes, defective lacrimation, and impaired pain and temperature perception. The disorder is inevitably fatal, with only 50% of patients reaching 40 years of age. HSAN3 has a high carrier frequency in the Ashkenazi Jewish population (summary by Morini et al., 2016). For a discussion of genetic heterogeneity of hereditary sensory and autonomic neuropathy, see HSAN1 (162400).  http://www.omim.org/entry/223900
From MedlinePlus Genetics
Familial dysautonomia is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called hereditary sensory and autonomic neuropathy, type III.

Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections, and difficulty maintaining body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which may cause a bluish appearance of the skin or lips (cyanosis) or fainting. This breath-holding behavior usually stops by age 6. Developmental milestones, such as walking and speech, are usually delayed, although some affected individuals show no signs of developmental delay.

Additional signs and symptoms in school-age children include bed wetting, episodes of vomiting, reduced sensitivity to temperature changes and pain, poor balance, abnormal curvature of the spine (scoliosis), poor bone quality and increased risk of bone fractures, and kidney and heart problems. Affected individuals also have poor regulation of blood pressure. They may experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. They can also have episodes of high blood pressure when nervous or excited, or during vomiting incidents. About one-third of children with familial dysautonomia have learning disabilities, such as a short attention span, that require special education classes. By adulthood, affected individuals often have increasing difficulties with balance and walking unaided. Other problems that may appear in adolescence or early adulthood include lung damage due to repeated infections, impaired kidney function, and worsening vision due to the shrinking size (atrophy) of optic nerves, which carry information from the eyes to the brain.  https://medlineplus.gov/genetics/condition/familial-dysautonomia

Clinical features

From HPO
Abnormal renal physiology
MedGen UID:
508816
Concept ID:
C0151746
Pathologic Function
An abnormal functionality of the kidney.
Glomerular sclerosis
MedGen UID:
61248
Concept ID:
C0178664
Disease or Syndrome
Accumulation of scar tissue within the glomerulus.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Tachycardia
MedGen UID:
21453
Concept ID:
C0039231
Finding
A rapid heartrate that exceeds the range of the normal resting heartrate for age.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Orthostatic hypotension
MedGen UID:
43803
Concept ID:
C0020651
Disease or Syndrome
A form of hypotension characterized by a sudden fall in blood pressure that occurs when a person assumes a standing position.
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
Incoordination
MedGen UID:
141714
Concept ID:
C0520966
Finding
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Decreased number of large peripheral myelinated nerve fibers
MedGen UID:
395303
Concept ID:
C1859606
Finding
A reduced number of large myelinated nerve fibers.
Neuropathic arthropathy
MedGen UID:
13919
Concept ID:
C0003892
Disease or Syndrome
Chronic progressive degeneration of the stress-bearing portion of a joint, with bizarre hypertrophic changes at the periphery. It is probably a complication of a variety of neurologic disorders, particularly tabes dorsalis, involving loss of sensation, which leads to relaxation of supporting structures and chronic instability of the joint. (Dorland, 27th ed)
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Recurrent infections due to aspiration
MedGen UID:
812615
Concept ID:
C3806285
Finding
Increased susceptibility to infections due to aspiration, as manifested by recurrent episodes of infections due to aspiration.
Decreased sensitivity to hypoxemia
MedGen UID:
812616
Concept ID:
C3806286
Finding
Reduced tendency to respond to a reduced concentration of oxygen in the blood by increasing respiration.
Increased blood urea nitrogen
MedGen UID:
760252
Concept ID:
C0151539
Finding
An increased amount of nitrogen in the form of urea in the blood.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Hypogeusia
MedGen UID:
57498
Concept ID:
C0151934
Finding
A decreased ability to perceive flavor.
Acrocyanosis
MedGen UID:
65138
Concept ID:
C0221347
Finding
Bluish discoloration of the skin of the hands or feet.
Episodic hyperhidrosis
MedGen UID:
387757
Concept ID:
C1857171
Finding
Intermittent episodes of abnormally increased perspiration.
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.
Decreased corneal reflex
MedGen UID:
57723
Concept ID:
C0151572
Finding
An abnormally reduced response to stimulation of the cornea (by touch, foreign body, blowing air). The corneal reflex (also known as the blink reflex, normally results in an involuntary blinking of the eyelids.
Recurrent corneal erosions
MedGen UID:
56353
Concept ID:
C0155119
Disease or Syndrome
The presence of recurrent corneal epithelial erosions. Although most corneal epithelial defects heal quickly, some may show recurrent ulcerations.
Alacrima
MedGen UID:
87488
Concept ID:
C0344505
Disease or Syndrome
Absence of tear secretion.
Pupillary hypersensitivity to parasympathomimetic agents
MedGen UID:
1052816
Concept ID:
CN378345
Finding
A higher than normal tendency of parasympathomimetic agents to induce miosis.

Professional guidelines

PubMed

Kazachkov M, Palma JA, Norcliffe-Kaufmann L, Bar-Aluma BE, Spalink CL, Barnes EP, Amoroso NE, Balou SM, Bess S, Chopra A, Condos R, Efrati O, Fitzgerald K, Fridman D, Goldenberg RM, Goldhaber A, Kaufman DA, Kothare SV, Levine J, Levy J, Lubinsky AS, Maayan C, Moy LC, Rivera PJ, Rodriguez AJ, Sokol G, Sloane MF, Tan T, Kaufmann H
Respir Med 2018 Aug;141:37-46. Epub 2018 Jun 21 doi: 10.1016/j.rmed.2018.06.017. PMID: 30053970Free PMC Article
Norcliffe-Kaufmann L, Slaugenhaupt SA, Kaufmann H
Prog Neurobiol 2017 May;152:131-148. Epub 2016 Jun 15 doi: 10.1016/j.pneurobio.2016.06.003. PMID: 27317387
Axelrod FB, Nachtigal R, Dancis J
Adv Pediatr 1974;21:75-96. PMID: 4217094

Curated

American College of Medical Genetics ACT Sheet, Carrier Screening ACT Sheet Ashkenazi Jewish Genetic Disorders

Recent clinical studies

Etiology

Gibbons CH, Levine T, Adler C, Bellaire B, Wang N, Stohl J, Agarwal P, Aldridge GM, Barboi A, Evidente VGH, Galasko D, Geschwind MD, Gonzalez-Duarte A, Gil R, Gudesblatt M, Isaacson SH, Kaufmann H, Khemani P, Kumar R, Lamotte G, Liu AJ, McFarland NR, Miglis M, Reynolds A, Sahagian GA, Saint-Hillaire MH, Schwartzbard JB, Singer W, Soileau MJ, Vernino S, Yerstein O, Freeman R
JAMA 2024 Apr 16;331(15):1298-1306. doi: 10.1001/jama.2024.0792. PMID: 38506839Free PMC Article
Wieling W, Kaufmann H, Claydon VE, van Wijnen VK, Harms MPM, Juraschek SP, Thijs RD
Lancet Neurol 2022 Aug;21(8):735-746. doi: 10.1016/S1474-4422(22)00169-7. PMID: 35841911Free PMC Article
Spencer TL, Watts L, Soni A, Pinedo-Villanueva R, Heegaard AM, Boyce AM, Javaid MK
J Clin Endocrinol Metab 2022 May 17;107(6):e2258-e2266. doi: 10.1210/clinem/dgac120. PMID: 35262711Free PMC Article
Kazachkov M, Palma JA, Norcliffe-Kaufmann L, Bar-Aluma BE, Spalink CL, Barnes EP, Amoroso NE, Balou SM, Bess S, Chopra A, Condos R, Efrati O, Fitzgerald K, Fridman D, Goldenberg RM, Goldhaber A, Kaufman DA, Kothare SV, Levine J, Levy J, Lubinsky AS, Maayan C, Moy LC, Rivera PJ, Rodriguez AJ, Sokol G, Sloane MF, Tan T, Kaufmann H
Respir Med 2018 Aug;141:37-46. Epub 2018 Jun 21 doi: 10.1016/j.rmed.2018.06.017. PMID: 30053970Free PMC Article
Axelrod FB, Hilz MJ
Semin Neurol 2003 Dec;23(4):381-90. doi: 10.1055/s-2004-817722. PMID: 15088259

Diagnosis

Gibbons CH, Levine T, Adler C, Bellaire B, Wang N, Stohl J, Agarwal P, Aldridge GM, Barboi A, Evidente VGH, Galasko D, Geschwind MD, Gonzalez-Duarte A, Gil R, Gudesblatt M, Isaacson SH, Kaufmann H, Khemani P, Kumar R, Lamotte G, Liu AJ, McFarland NR, Miglis M, Reynolds A, Sahagian GA, Saint-Hillaire MH, Schwartzbard JB, Singer W, Soileau MJ, Vernino S, Yerstein O, Freeman R
JAMA 2024 Apr 16;331(15):1298-1306. doi: 10.1001/jama.2024.0792. PMID: 38506839Free PMC Article
Younger DS
Handb Clin Neurol 2023;195:55-102. doi: 10.1016/B978-0-323-98818-6.00020-0. PMID: 37562886
Rand CM, Weese-Mayer DE
Clin Auton Res 2023 Jun;33(3):211-213. doi: 10.1007/s10286-023-00957-7. PMID: 37273037Free PMC Article
Wieling W, Kaufmann H, Claydon VE, van Wijnen VK, Harms MPM, Juraschek SP, Thijs RD
Lancet Neurol 2022 Aug;21(8):735-746. doi: 10.1016/S1474-4422(22)00169-7. PMID: 35841911Free PMC Article
Axelrod FB, Hilz MJ
Semin Neurol 2003 Dec;23(4):381-90. doi: 10.1055/s-2004-817722. PMID: 15088259

Therapy

Ishigami Y, Wong MS, Martí-Gómez C, Ayaz A, Kooshkbaghi M, Hanson SM, McCandlish DM, Krainer AR, Kinney JB
Nat Commun 2024 Feb 29;15(1):1880. doi: 10.1038/s41467-024-46090-5. PMID: 38424098Free PMC Article
Wieling W, Kaufmann H, Claydon VE, van Wijnen VK, Harms MPM, Juraschek SP, Thijs RD
Lancet Neurol 2022 Aug;21(8):735-746. doi: 10.1016/S1474-4422(22)00169-7. PMID: 35841911Free PMC Article
Palma JA, Norcliffe-Kaufmann L, Fuente-Mora C, Percival L, Mendoza-Santiesteban C, Kaufmann H
Expert Opin Pharmacother 2014 Dec;15(18):2653-71. Epub 2014 Oct 17 doi: 10.1517/14656566.2014.970530. PMID: 25323828Free PMC Article
Moss AA, Goldberg HI
CRC Crit Rev Radiol Sci 1972;3(3):363-87. PMID: 4146635
Rubin MI
Pediatr Clin North Am 1964 May;11(2):431-63. doi: 10.1016/s0031-3955(16)31556-5. PMID: 4875684

Prognosis

Wieling W, Kaufmann H, Claydon VE, van Wijnen VK, Harms MPM, Juraschek SP, Thijs RD
Lancet Neurol 2022 Aug;21(8):735-746. doi: 10.1016/S1474-4422(22)00169-7. PMID: 35841911Free PMC Article
Axelrod FB
Muscle Nerve 2004 Mar;29(3):352-63. doi: 10.1002/mus.10499. PMID: 14981733
Gilbert F
Genet Test 2001 Summer;5(2):83-5. doi: 10.1089/109065701753145510. PMID: 11551107
Sarwark JF, Kramer A
Curr Opin Pediatr 1998 Feb;10(1):82-6. doi: 10.1097/00008480-199802000-00017. PMID: 9529645
Axelrod FB, Nachtigal R, Dancis J
Adv Pediatr 1974;21:75-96. PMID: 4217094

Clinical prediction guides

Cheney AM, Costello SM, Pinkham NV, Waldum A, Broadaway SC, Cotrina-Vidal M, Mergy M, Tripet B, Kominsky DJ, Grifka-Walk HM, Kaufmann H, Norcliffe-Kaufmann L, Peach JT, Bothner B, Lefcort F, Copié V, Walk ST
Nat Commun 2023 Jan 13;14(1):218. doi: 10.1038/s41467-023-35787-8. PMID: 36639365Free PMC Article
Veazie S, Peterson K, Ansari Y, Chung KA, Gibbons CH, Raj SR, Helfand M
Cochrane Database Syst Rev 2021 May 17;5(5):CD012868. doi: 10.1002/14651858.CD012868.pub2. PMID: 34000076Free PMC Article
Singh K, Palma JA, Kaufmann H, Tkachenko N, Norcliffe-Kaufmann L, Spalink C, Kazachkov M, Kothare SV
Sleep Med 2018 May;45:33-38. Epub 2018 Feb 7 doi: 10.1016/j.sleep.2017.12.013. PMID: 29680425Free PMC Article
Fuente Mora C, Palma JA, Kaufmann H, Norcliffe-Kaufmann L
J Cereb Blood Flow Metab 2017 Jul;37(7):2414-2422. Epub 2016 Jan 1 doi: 10.1177/0271678X16667524. PMID: 27613312Free PMC Article
Newman NJ, Biousse V
Eye (Lond) 2004 Nov;18(11):1144-60. doi: 10.1038/sj.eye.6701591. PMID: 15534600

Recent systematic reviews

Veazie S, Peterson K, Ansari Y, Chung KA, Gibbons CH, Raj SR, Helfand M
Cochrane Database Syst Rev 2021 May 17;5(5):CD012868. doi: 10.1002/14651858.CD012868.pub2. PMID: 34000076Free PMC Article
Gutierrez J, Palma JA, Kaufmann H
Semin Neurol 2020 Oct;40(5):580-590. Epub 2020 Sep 9 doi: 10.1055/s-0040-1713843. PMID: 32906171Free PMC Article
Kazachkov M, Palma JA, Norcliffe-Kaufmann L, Bar-Aluma BE, Spalink CL, Barnes EP, Amoroso NE, Balou SM, Bess S, Chopra A, Condos R, Efrati O, Fitzgerald K, Fridman D, Goldenberg RM, Goldhaber A, Kaufman DA, Kothare SV, Levine J, Levy J, Lubinsky AS, Maayan C, Moy LC, Rivera PJ, Rodriguez AJ, Sokol G, Sloane MF, Tan T, Kaufmann H
Respir Med 2018 Aug;141:37-46. Epub 2018 Jun 21 doi: 10.1016/j.rmed.2018.06.017. PMID: 30053970Free PMC Article
Weingarten TN, Sprung J, Burgher AH
Eur J Anaesthesiol 2007 Apr;24(4):309-16. Epub 2007 Jan 4 doi: 10.1017/S026502150600192X. PMID: 17202006

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2011
      American College of Medical Genetics ACT Sheet, Carrier Screening ACT Sheet Ashkenazi Jewish Genetic Disorders

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...