Changes: Familial dysautonomia

Familial dysautonomia
	Classification and external resources
	Template:Px; Facial features of a patient with familial dysautonomia over time. Note flattening of upper lip. By age 10 years prominence of lower jaw is apparent and by age 19 years there is mild erosion of right nostril due to inadvertent self-mutilation.
ICD-10	G901
ICD-9	742.8
OMIM	223900
DiseasesDB	11631
eMedicine	oph/678
MeSH	D004402
GeneReviews	Template:Citation/make link

Latest revision as of 02:04, 7 July 2012

Clinical: Approaches · Group therapy · Techniques · Types of problem · Areas of specialism · Taxonomies · Therapeutic issues · Modes of delivery · Model translation project · Personal experiences ·

{

This article is in need of attention from a psychologist/academic expert on the subject.
Please help recruit one, or improve this page yourself if you are qualified.
This banner appears on articles that are weak and whose contents should be approached with academic caution.

Familial dysautonomia (FD), sometimes called Riley–Day syndrome^[1] and hereditary sensory and autonomic neuropathy type III (HSAN-III) — is a disorder of the autonomic nervous system which affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system resulting in variable symptoms including: insensitivity to pain, inability to produce tears, poor growth, and labile blood pressure (episodic hypertension and postural hypotension). People with FD have frequent vomiting crises, pneumonia, problems with speech and movement, difficulty swallowing, inappropriate perception of heat, pain, and taste, as well as unstable blood pressure and gastrointestinal dysmotility. FD does not affect intelligence. Originally reported by Conrad Milton Riley and Richard Lawrence Day in 1949,^[2] FD is one example of a group of disorders known as hereditary sensory and autonomic neuropathies HSAN.^[3] All HSAN are characterized by widespread sensory dysfunction and variable autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. The disorders are believed to be genetically distinct from each other.

Incidence

Familial dysautonomia is seen almost exclusively in Ashkenazi Jews and is inherited in an autosomal recessive fashion. Both parents must be carriers in order for a child to be affected. The carrier frequency in Jewish individuals of Eastern European (Ashkenazi) ancestry is about 1/30, while the carrier frequency in non-Jewish individuals is unknown. If both parents are carriers, there is a one in four, or 25%, chance with each pregnancy for an affected child. Genetic counseling and genetic testing is recommended for families who may be carriers of familial dysautonomia.^{[citation needed]}

Worldwide, there have been approximately 600 diagnoses recorded since discovery of the disease, with approximately 350 of them still living.^[4]

Etiology

Familial Dysautonomia, is the result of mutations in IKBKAP gene on chromosome 9, which encodes for the IKAP protein (IkB kinase complex associated protein). There have been three mutations in IKBKAP identified in individuals with FD. The most common FD-causing mutation occurs in intron 20 of the donor gene. Conversion of T-->C in intron 20 of the donor gene resulted in shift splicing that generates an IKAP transcript lacking exon 20. Translation of this mRNA results in a truncated protein lacking all of the amino acids encoded in exons 20-37. Another less common mutation is a G-->C conversion resulting in one amino acid mutation in 696, where Proline substitutes normal Arginine. The decreased amount of functional IKAP protein in cells causes Familial Dysautonomia.

Diagnosis

This section does not cite any references or sources.
Please help improve this section by adding citations to reliable sources. (help, get involved!)
Unverifiable material may be challenged and removed.

This article has been tagged since March 2009.

Symptoms

Symptoms displayed by a baby with FD might include:

The most distinctive clinical feature is absence of overflow tears with emotional crying after age 7 months. This symptom can manifest less dramatically as persistent bilateral eye irritation.
High prevalence of breech presentation
Weak or absent suck and poor tone
Poor suck and misdirected swallowing
Red blotching of skin

Symptoms in an older child with FD might include:

Delayed speech and walking
Unsteady gait
Spinal curvature
Corneal abrasion
Less perception in pain or temperature with nervous system.
Poor growth
Erratic or unstable blood pressure.
Red puffy hands
Dysautonomia crisis: constellation of symptoms response to physical and emotional stress; usually accompanied by vomiting, increased heart rate, increase in blood pressure, sweating, drooling, blotching of the skin and a negative change in personality.

Clinical Diagnosis

Autorecessive — Autosomal recessive inheritance

A clinical diagnosis of FD is supported by a constellation of criteria:

Parents of Ashkenazi Jewish Background
No fungiform papillae on the tongue
Decreased deep tendon reflexes
Lack of an axon flare following intradermal histamine
No overflow tears with emotional crying

Genetic Testing

Genetic testing is performed on a small sample of blood from the tested individual. The DNA is examined with a designed probe specific to the known mutations. The accuracy of the test is above 99%. Dr. Anat Blumenfeld of the Hadasah Medical center in Jerusalem identified chromosome number 9 as the responsible chromosome.

Prenatal Testing

Familial Dysautonomia is inherited in an autosomal recessive pattern, which means 2 copies of the gene in each cell are altered. If both parents are shown to be carriers by genetic testing, there is a 25% chance that the child will produce FD. Prenatal diagnosis for pregnancies at increased risk for FD by amniocentesis (for 14–17 weeks) or chorionic villus sampling (for 10–11 weeks) is possible.

Treatment and treatment locations

There currently is no cure for FD and death occurs in 50% of affected individuals by age 30. There are only two treatment centers, one at New York University Hospital^[5] and one at the Hadassah Hospital in Israel. ^[6] One is being planned for the San Francisco area.^[7]

The survival rate and quality of life has increased since the mid 80's mostly due to greater understanding of the most dangerous symptoms. At present, FD patients can be expected to function independently if treatment is begun early and major disabilities avoided.

A major issue has been Aspiration Pneumonias, where food or regurgitated stomach content would be aspirated into the lungs causing infections. Fundoplications (by preventing regurgitation) and gastrostomy tubes (to provide non oral nutrition) have reduced the frequency of hospitalization.

Other issues which can be treated include FD Crises, Scoliosis, and various eye conditions due to limited or no tears.

An FD crisis is the body's loss of control of various Autonomic nervous system functions including blood pressure, heartrate, and body temperature. Both short term and chronic periodic high or low blood pressure have consequences and medication is used to stabilize blood pressure.

Treatment of Manifestations

File:Kyphoscoliosis hereditary sensory autonomic neuropathy III.jpg

Kyphoscoliosis in a 10-year-old girl with HSANIII.

Although the FD-causing gene has been identified and it seems to have tissue specific expression, there is no definitive treatment at present. Treatment of FD remains preventative, symptomatic and supportive. FD does not express itself in a consistent manner. The type and severity of symptoms displayed vary among patients and even at different ages on the same patients. So patients should have specialized individual treatment plans. Medications are used to control vomiting, eye dryness, and blood pressure. There are some commonly needed treatments including:

Artificial tears: using eye drop containing artificial tear solutions (methylcellulose)
Feeding: Maintenance of adequate nutrition, avoidance of aspiration; thickened formula and different shaped nipples are used for baby.
Daily chest physiotherapy (nebulization, bronchodilators, and postural drainage): for Chronic lung disease from recurrent aspiration pneumonia
Special drug management of autonomic manifestations such as vomiting: intravenous or rectal diazepam (0.2 mg/kg q3h) and rectal chloral hydrate (30 mg/kg q6h)
Protecting the child from injury (coping with decreased taste, temperature and pain perception)
Combating orthostatic hypotension: hydration, leg exercise, frequent small meals, a high-salt diet, and drugs such as fludrocortisone.
Treatment of orthopedic problems (tibial torsion and spinal curvature)
Compensating for labile blood pressures

There is no cure for this genetic disorder.

Therapies under investigation

It is noted that in cell lines derived from heterozygous carriers of FD who display a normal phenotype, there are decreased levels of the wild-type IKAP transcript and also functional IKAP protein respectively. This would suggest that increasing the amount of the wild-type IKAP transcript may improve the manifestation in patients with FD.

Prognosis

The outlook for patients with FD depends on the particular diagnostic category. Patients with chronic, progressive, generalized dysautonomia in the setting of central nervous system degeneration have a generally poor long-term prognosis. Death can occur from pneumonia, acute respiratory failure, or sudden cardiopulmonary arrest in such patients. (There needs to be a transition here to interventions re: eye care. This comment below has nothing to do with prognosis, but supportive care.) Educate parents and patients regarding daily eye care and early warning signs of corneal problems as well as use of punctual cautery. This education has resulted in decreased corneal scarring and need for more aggressive surgical measures such as tarsorrhaphy, conjunctival flaps, and corneal transplants.

Future

In January 2001, researchers at Fordham University and Massachusetts General Hospital simultaneously reported finding the genetic mutation that causes FD, a discovery that opens the door to many diagnostic and treatment possibilities.^[8]^[9]

Despite that it probably would not happen in the near future, some expect that stem-cell therapy will result. Eventually, treatment could be given in utero.^{[citation needed]}

While that may be years ahead, genetic screening became available around April 2001, enabling Ashkenazi Jews to find out if they are carriers. Screening organization Dor Yeshorim offers testing as part of its panel, which also includes Tay-Sachs disease and cystic fibrosis.

In the meantime more research into treatments are being funded by the foundations that exist. These foundations are organized and run by parents of those with FD. There is no governmental support beyond recognizing those diagnosed with FD as eligible for certain programs.^[10]

References

↑ pediatriconcall.com
↑ Riley CM, Day RL, Greely D, Langford WS (1949). Central autonomic dysfunction with defective lacrimation. Pediatrics 3 (4): 468–77.
↑ Axelrod FB (2002). Hereditary sensory and autonomic neuropathies. Familial dysautonomia and other HSANs. Clin Auton Res Suppl 1 (7): I2–14.
↑ http://www.familialdysautonomia.org/history.php
↑ Dysautonomia Treatment and Evaluation Center
↑ Familial Dysautonomia Center
↑ San Francisco To Get a Genetics Center - Forward.com. URL accessed on 2007-11-02.
↑ Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, Ekstein J, Rubin BY (2001). Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet 68 (3): 753–8.
↑ Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, Liebert CB, Chadwick B, Idelson M, Reznik L, Robbins C, Makalowska I, Brownstein M, Krappmann D, Scheidereit C, Maayan C, Axelrod FB, Gusella JF (2001). Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am J Hum Genet 68 (3): 598–605.
↑ Benefits for people with FD - from Dysautonomia foundation

External links

GeneReviews/NCBI/NIH/UW entry on Familial Dysautonomia

Support organizations

This page uses Creative Commons Licensed content from Wikipedia (view authors).

[1] triconcall.com

[2] Riley CM, Day RL, Greely D, Langford WS (1949). Central autonomic dysfunction with defective lacrimation. Pediatrics 3 (4): 468–77.

[3] Axelrod FB (2002). Hereditary sensory and autonomic neuropathies. Familial dysautonomia and other HSANs. Clin Auton Res Suppl 1 (7): I2–14.

[4] ttp://www.familialdysautonomia.org/history.php

[5] Dysautonomia Treatment and Evaluation Center

[6] Familial Dysautonomia Center

[7] San Francisco To Get a Genetics Center - Forward.com. URL accessed on 2007-11-02.

[8] Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, Ekstein J, Rubin BY (2001). Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet 68 (3): 753–8.

[9] Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, Liebert CB, Chadwick B, Idelson M, Reznik L, Robbins C, Makalowska I, Brownstein M, Krappmann D, Scheidereit C, Maayan C, Axelrod FB, Gusella JF (2001). Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am J Hum Genet 68 (3): 598–605.

[10] Benefits for people with FD - from Dysautonomia foundation

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

@@ Line 1: / Line 1: @@
 {{ClinPsy}}
+{{{expert}}
-{{DiseaseDisorder infobox |
+{{Infobox disease |
  Name = Familial dysautonomia |
- [[Image = Autorecessive.svg|Thumb|150px|]]
+ Image = Riley day.jpg|
+ Caption = Facial features of a patient with familial dysautonomia over time. Note flattening of upper lip. By age 10 years prominence of lower jaw is apparent and by age 19 years there is mild erosion of right nostril due to inadvertent self-mutilation.|
- Caption = [[Recessive gene|Autosomal recessive]] inheritance |
  ICD10 = {{ICD10|G|90|1|g|90}} |
  ICD9 = {{ICD9|742.8}} |
@@ Line 12: / Line 13: @@
  eMedicineSubj = oph |
  eMedicineTopic = 678 |
+ MeshID = D004402 |
+ GeneReviewsNBK   = NBK1180 |
+ GeneReviewsName = Familial dysautonomia
 }}
+'''Familial dysautonomia''' (FD), sometimes called '''Riley–Day syndrome'''<ref>[http://www.pediatriconcall.com/fordoctor/CaseReports/hsan.asp pediatriconcall.com]</ref> and '''[[hereditary sensory and autonomic neuropathy]] type III''' (HSAN-III) — is a disorder of the [[autonomic nervous system]] which affects the development and survival of sensory, sympathetic and some parasympathetic [[neurons]] in the autonomic and sensory [[nervous system]] resulting in variable symptoms including: [[Pain#Insensitivity to pain|insensitivity to pain]], inability to produce tears, poor growth, and labile blood pressure (episodic hypertension and postural hypotension). People with FD have frequent vomiting crises, pneumonia, problems with speech and movement, difficulty swallowing, inappropriate perception of heat, pain, and taste, as well as unstable blood pressure and gastrointestinal dysmotility. FD does not affect intelligence. Originally reported by Conrad Milton Riley and Richard Lawrence Day in 1949,<ref>{{cite journal | author=Riley CM, Day RL, Greely D, Langford WS | title=Central autonomic dysfunction with defective lacrimation | journal=Pediatrics | year=1949 | pages=468–77 | volume=3 |issue=4 |pmid=18118947 }}</ref> FD is one example of a group of disorders known as hereditary sensory and autonomic neuropathies [[HSAN]].<ref>{{cite journal | author=Axelrod FB | title=Hereditary sensory and autonomic neuropathies. Familial dysautonomia and other HSANs | series=12 | journal=Clin Auton Res | year=2002 | pages=I2–14 | issue=7 | volume=Suppl 1 | pmid=12102459 | doi=10.1007/s102860200014}}</ref> All HSAN are characterized by widespread sensory dysfunction and variable autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. The disorders are believed to be genetically distinct from each other.
-'''Familial dysautonomia''', or '''FD''', is a disorder of the [[autonomic nervous system]] which affects the development and survival of sensory, sympathetic and some parasympathetic [[neurons]] in the autonomic and sensory [[nervous system]] resulting in variable symptoms including: insensitivity to pain, inability to produce tears, poor growth, and labile blood pressure (episodic hypertension and postural hypotension). People with FD have frequent vomiting crises, pneumonia, problems with speech and movement, difficulty swallowing, inappropriate perception of heat, pain, and taste, as well as unstable blood pressure and gastrointestinal dysmotility. FD does not affect intelligence. Originally reported by Riley, ''et al.'' in 1949, FD is one example of a group of disorders known as hereditary sensory and autonomic neuropathies [[HSAN]]. All HSAN are characterized by widespread sensory dysfunction and variable autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. The disorders are believed to be genetically distinct from each other.
 ==Incidence==
-FD is seen almost exclusively in [[Ashkenazi]] Jews and is inherited in an autosomal [[recessive]] fashion. Both parents must be carriers in order for a child to be affected. The carrier frequency in Jewish individuals of Eastern European (Ashkenazi) ancestry is about 1/30, while the carrier frequency in non-Jewish individuals is about 1/3000. If both parents are carriers, there is a one in four, or 25%, chance with each pregnancy for an affected child. [[Genetic counseling]] and [[genetic testing]] is recommended for families who may be carriers of familial dysautonomia.
+Familial dysautonomia is seen almost exclusively in [[Ashkenazi]] Jews and is inherited in an autosomal [[recessive]] fashion. Both parents must be carriers in order for a child to be affected. The carrier frequency in Jewish individuals of Eastern European (Ashkenazi) ancestry is about 1/30, while the carrier frequency in non-Jewish individuals is unknown. If both parents are carriers, there is a one in four, or 25%, chance with each pregnancy for an affected child. [[Genetic counseling]] and [[genetic testing]] is recommended for families who may be carriers of familial dysautonomia.{{Citation needed|date=March 2009}}
+Worldwide, there have been approximately 600 diagnoses recorded since discovery of the disease, with approximately 350 of them still living.<ref>http://www.familialdysautonomia.org/history.php</ref>
-There have been 590 cases in total. Currently there are 350 people living with this condition worldwide.
 ==Etiology==
 Familial Dysautonomia, is the result of mutations in [[IKBKAP]] gene on [[chromosome 9]], which encodes for the [[IKAP protein]] (IkB kinase complex associated protein). There have been three mutations in IKBKAP identified in individuals with FD. The most common FD-causing mutation occurs in [[intron]] 20 of the donor gene. Conversion of T-->C in intron 20 of the donor gene resulted in shift splicing that generates an IKAP transcript lacking [[exon]] 20. Translation of this mRNA results in a truncated protein lacking all of the amino acids encoded in exons 20-37. Another less common mutation is a G-->C conversion resulting in one amino acid mutation in 696, where [[Proline]] substitutes normal [[Arginine]]. The decreased amount of functional IKAP protein in cells causes Familial Dysautonomia.
 ==Diagnosis==
+{{Unreferenced section|date=March 2009}}
 ===Symptoms===
 Symptoms displayed by a baby with FD might include:
-# The most distinctive clinical feature is absence of overflow tears with emotional crying after age 7 months.
+# The most distinctive clinical feature is absence of overflow tears with emotional crying after age 7 months. This symptom can manifest less dramatically as persistent bilateral eye irritation.
 # High prevalence of breech presentation
 # Weak or absent suck and poor tone
@@ Line 49: / Line 54: @@
 ===Clinical Diagnosis===
+[[Image:Autorecessive.svg|200px|thumb|[[Recessive gene|Autosomal recessive]] inheritance]]
 A clinical diagnosis of FD is supported by a constellation of criteria:
@@ Line 58: / Line 64: @@
 ===Genetic Testing===
+Genetic testing is performed on a small sample of blood from the tested individual. The [[DNA]] is examined with a designed probe specific to the known mutations. The accuracy of the test is above 99%. Dr. [[Anat Blumenfeld]] of the Hadasah Medical center in Jerusalem identified chromosome number 9 as the responsible chromosome.
-Genetic testing is performed on a small sample of blood from the tested individual. The [[DNA]] is examined with a designed probe specific to the known mutations. The accuracy of the test is above 99%.
 ===Prenatal Testing===
-Familial Dysautonomia is inherited in an autosomal [[recessive]] pattern, which means 2 copies of the gene in each cell are altered. If both parents are shown to be carriers by generic testing, there is a 25% chance that the child will produce FD. Prenatal diagnosis for pregnancies at increased risk for FD by [[amniocentesis]] (for 14-17 weeks) or [[chorionic villus sampling]] (for 10-11 weeks) is possible.
+Familial Dysautonomia is inherited in an autosomal [[recessive]] pattern, which means 2 copies of the gene in each cell are altered. If both parents are shown to be carriers by genetic testing, there is a 25% chance that the child will produce FD. Prenatal diagnosis for pregnancies at increased risk for FD by [[amniocentesis]] (for 14–17 weeks) or [[chorionic villus sampling]] (for 10–11 weeks) is possible.
-==Treatment and Treatment Locations==
+==Treatment and treatment locations==
-There currently is no cure for FD and death occurs in 50% of affected individuals by age 30. There are only two treatment centers
+There currently is no cure for FD and death occurs in 50% of affected individuals by age 30. There are only two treatment centers,
-One at New York University Hospital [http://www.med.nyu.edu/fd/ Dysautonomia Treatment and Evaluation Center] and one at the Hadassah Hospital [http://www.hadassah.org.il/English/Eng_SubNavBar/Departments/Medical+departments/Pediatric+Mount+Scopus/FAMILIAL+DYSAUTONOMIA+CENTER.htm. Familial Dysautonomia Center]. One is being planned for the San Francisco area [http://www.forward.com/articles/3747 Forward Article]
+one at [[New York University Hospital]]<ref>[http://www.med.nyu.edu/fd/ Dysautonomia Treatment and Evaluation Center]</ref> and one at the [[Hadassah Hospital]] in [[Israel]].
+<ref>[http://www.hadassah.org.il/English/Eng_SubNavBar/Departments/Medical+departments/Pediatric+Mount+Scopus/FAMILIAL+DYSAUTONOMIA+CENTER.htm Familial Dysautonomia Center]</ref> One is being planned for the San Francisco area.<ref>{{cite web |url=http://www.forward.com/articles/2528/ |title=San Francisco To Get a Genetics Center - Forward.com |accessdate=2007-11-02 |format= |work=}}</ref>
 The survival rate and quality of life has increased since the mid 80's mostly due to greater understanding of the most dangerous symptoms.
 At present, FD patients can be expected to function independently if treatment is begun early and major disabilities avoided.
-A major issue has been Aspiration Pneumonias, where food or regurgitated stomach content would be aspirated into the lungs causing infections. [[Nissen fundoplication|Fundoplacations]] (by preventing regurgitation) and gastrostomy tubes (to provide non oral nutrition) have reduced the frequency of hospitalization.
+A major issue has been Aspiration Pneumonias, where food or regurgitated stomach content would be aspirated into the lungs causing infections. [[Nissen fundoplication|Fundoplications]] (by preventing regurgitation) and gastrostomy tubes (to provide non oral nutrition) have reduced the frequency of hospitalization.
 Other issues which can be treated include FD Crises, [[Scoliosis]], and various eye conditions due to limited or no tears.
-An FD crisis is the body's loss of control of various [Autonomic nervous system] functions including blood pressure, heartrate, and body temperature. Both short term and chronic periodic high or low blood pressure have consequences and medication is used to stabilize blood pressure.
+An FD crisis is the body's loss of control of various [[Autonomic nervous system]] functions including blood pressure, heartrate, and body temperature. Both short term and chronic periodic high or low blood pressure have consequences and medication is used to stabilize blood pressure.
 ===Treatment of Manifestations===
+[[Image:Kyphoscoliosis hereditary sensory autonomic neuropathy III.jpg|thumb|[[Kyphoscoliosis]] in a 10-year-old girl with HSANIII.]]
-Although the FD-causing gene has been identifies and it seems to have tissue specific expression, there is no definitive treatment at present.
+Although the FD-causing gene has been identified and it seems to have tissue specific expression, there is no definitive treatment at present.
 Treatment of FD remains preventative, symptomatic and supportive. FD does not express itself in a consistent manner. The type and severity of symptoms displayed vary among patients and even at different ages on the same patients. So patients should have specialized individual treatment plans. Medications are used to control vomiting, eye dryness, and [[blood pressure]]. There are some commonly needed treatments including:
 # Artificial tears: using eye drop containing artificial tear solutions (methylcellulose)
 # Feeding: Maintenance of adequate nutrition, avoidance of aspiration; thickened formula and different shaped nipples are used for baby.
-# Daily chest [[physiotherapy]] (nebulization, [[bronchodilators]], and posural drainage): for Chronic lung disease from recurrent aspiration [[pneumonia]]
+# Daily chest [[physiotherapy]] (nebulization, [[bronchodilators]], and postural drainage): for Chronic lung disease from recurrent aspiration [[pneumonia]]
-# Special drug management of autonomic manifestations such as vomiting: intravenous or rectal [[diazepam]] (0.2 mg/kg q3h) and rectal chloral hydrate (30 mg/kg q6h)
+# Special drug management of autonomic manifestations such as vomiting: intravenous or rectal [[diazepam]] (0.2&nbsp;mg/kg q3h) and rectal chloral hydrate (30&nbsp;mg/kg q6h)
 # Protecting the child from injury (coping with decreased taste, temperature and pain perception)
 # Combating [[orthostatic hypotension]]: hydration, leg exercise, frequent small meals, a high-salt diet, and drugs such as [[fludrocortisone]].
 # Treatment of orthopedic problems (tibial torsion and spinal curvature)
 # Compensating for labile blood pressures
+There is no cure for this genetic disorder.
 ===Therapies under investigation===
 It is noted that in cell lines derived from [[heterozygous]] carriers of FD who display a normal phenotype, there are decreased levels of the wild-type IKAP transcript and also functional [[IKAP protein]] respectively. This would suggest that increasing the amount of the wild-type IKAP transcript may improve the manifestation in patients with FD.
-Application of [[tocotrienol]]s in the treatment of FD was initiated in the FD research lab at Fordham University in Bronx. In vitro supplementation of [[tocotrienol]]s elevated the expression of IKAP transcripts as well as the amount of induced functional [[IKAP protein]] in [[homozygous]] cell lines derived from FD patients. This observed result further suggests the value of therapeutic approaches to lessen suffered symptoms of FD patients by elevating cellular level of functional IKAP which can be induced by [[tocotrienol]]s.
-One form of therapy under investigation is [[electrolyte]] therapy for refractory seizures common among FD carriers. See [[Ceralyte]]<ref name= Ochoa>{{cite journal | author = Ochoa, Juan G. MD | title = Electrolyte Therapy for Refractory Seizures in Familial Dysautonomia | journal = Epilepsia | volume = 45 | pages =  1461-1462 | year = 2004}}</ref>
 ==Prognosis==
-The outlook for patients with FD depends on the particular diagnostic category. Patients with chronic, progressive, generalized [[dysautonomia]] in the setting of central nervous system degeneration have a generally poor long-term [[prognosis]]. Death can occur from [[pneumonia]], acute respiratory failure, or sudden cardiopulmonary arrest in such patients.
+The outlook for patients with FD depends on the particular diagnostic category. Patients with chronic, progressive, generalized [[dysautonomia]] in the setting of central nervous system degeneration have a generally poor long-term [[prognosis]]. Death can occur from [[pneumonia]], acute respiratory failure, or sudden cardiopulmonary arrest in such patients.  (There needs to be a transition here to interventions re:  eye care.  This comment below has nothing to do with prognosis, but supportive care.)
 Educate parents and patients regarding daily eye care and early warning signs of corneal problems as well as use of punctual cautery. This education has resulted in decreased corneal scarring and need for more aggressive surgical measures such as [[tarsorrhaphy]], conjunctival flaps, and [[corneal transplant]]s.
-==The Future==
+==Future==
+In January 2001, researchers at [[Fordham University]] and [[Massachusetts General Hospital]] simultaneously reported finding the genetic mutation that causes FD, a discovery that opens the door to many diagnostic and treatment possibilities.<ref>{{cite journal | author=Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, Ekstein J, Rubin BY | title=Familial dysautonomia is caused by mutations of the IKAP gene | journal=Am J Hum Genet | year=2001 | pages=753–8 | volume=68 | issue=3 | pmid=11179021 | doi=10.1086/318808 | pmc=1274486}}</ref><ref>{{cite journal | author=Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, Liebert CB, Chadwick B, Idelson M, Reznik L, Robbins C, Makalowska I, Brownstein M, Krappmann D, Scheidereit C, Maayan C, Axelrod FB, Gusella JF | title=Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia | journal=Am J Hum Genet | year=2001 | pages=598–605 | volume=68 | issue=3 | pmid=11179008 | doi=10.1086/318810 | pmc=1274473}}</ref>
-In January of 2001, researchers at [[Massachusetts General Hospital]] isolated the FD gene, a discovery that opens the door to many diagnostic and treatment possibilities.
-Although it probably won't happen for five or 10 years, some expect that stem-cell therapy will result. Eventually, treatment could be given in utero.
+Despite that it probably would not happen in the near future, some expect that stem-cell therapy will result. Eventually, treatment could be given in utero.{{Citation needed|reason="some expect" is inappropriate without a source, although both sentences should be sourced, otherwise they are speculation and should be deleted.|date=July 2010}}
-While that may be years ahead, genetic screening became available around April 2001, enabling Ashkenazi Jews to find out if they are carriers.
+While that may be years ahead, genetic screening became available around April 2001, enabling Ashkenazi Jews to find out if they are carriers. Screening organization [[Dor Yeshorim]] offers testing as part of its panel, which also includes [[Tay-Sachs disease]] and [[cystic fibrosis]].
-In the mean time more research into treatments are being funded by the foundations that exist. These foundation are organized and run by parents of those with FD. There is very limited governmental support beyond recognizing those diagnosed with FD as eligible for certain programs.
+In the meantime more research into treatments are being funded by the foundations that exist. These foundations are organized and run by parents of those with FD. There is no governmental support beyond recognizing those diagnosed with FD as eligible for certain programs.<ref>[http://www.familialdysautonomia.org/resguide/chapter4.htm Benefits for people with FD] - from [[Dysautonomia foundation]]</ref>
+==See also==
+*[[Hereditary sensory and autonomic neuropathy]] (HSAN)
+**[[Congenital insensitivity to pain with anhidrosis]] (CIPA), HSAN Type IV
+*[[Congenital insensitivity to pain]]
+*[[Dysautonomia]]
+*[[Medical genetics of Ashkenazi Jews]]
 ==References==
+{{Reflist|2}}
-# {{cite journal | author=Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, Ekstein J, Rubin BY | title=Familial dysautonomia is caused by mutations of the IKAP gene | journal=Am J Hum Genet | year=2001 | pages=753-8 | volume=68 | issue=3 | id=PMID 11179021}}
-# {{cite journal | author=Axelrod FB, Hilz MJ | title=Inherited autonomic neuropathies | journal=Semin Neurol | year=2003 | pages=381-90 | volume=23 | issue=4 | id=PMID 15088259}}
-# {{cite journal | author=Axelrod FB | title=Familial dysautonomia | journal=Muscle Nerve | year=2004 | pages=352-63 | volume=29 | issue=3 | id=PMID 14981733}}
-# {{cite journal | author=Axelrod FB | title=Hereditary sensory and autonomic neuropathies. Familial dysautonomia and other HSANs | journal=Clin Auton Res | year=2002 | pages=I2-14 | volume=12 Suppl 1 | id=PMID 12102459}}
-# {{cite journal | author=Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, Liebert CB, Chadwick B, Idelson M, Reznik L, Robbins C, Makalowska I, Brownstein M, Krappmann D, Scheidereit C, Maayan C, Axelrod FB, Gusella JF | title=Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia | journal=Am J Hum Genet | year=2001 | pages=598-605 | volume=68 | issue=3 | id=PMID 11179008}}
-# {{cite journal | author=Slaugenhaupt SA, Gusella JF | title=Familial dysautonomia | journal=Curr Opin Genet Dev | year=2002 | pages=307-11 | volume=12 | issue=3 | id=PMID 12076674}}
-# {{cite journal | author=Axelrod FB, Nachtigal R, Dancis J |title=Familial dysautonomia: diagnosis, pathogenesis and management | journal=Adv Pediatr | year=1974 | pages=75-96 | volume=21 | id=PMID: 4217094}}
-# {{cite journal | author=Brunt PW, McKusick VA. | title=Familial dysautonomia. A report of genetic and clinical studies, with a review of the literature | journal=Medicine (Baltimore) | year=1970 September | pages=343-74 | volume=49 |issue=5 | id=PMID: 4322121}}
-# {{cite journal | author=Riley CM, Day RL, Greely D, Langford WS | title=Central autonomic dysfunction with defective lacrimation | journal=Pediatrics | year=1949 | pages=468-77 | volume=3}}
-# {{cite journal | author=Axelrod FB | title=Familial Dysautonomia | journal=Robertson D, Low PA, Polinsky RJ (Eds.), Primer on the Autonomic Nervous System, Academic Press, San Diego | year=1996 | pages=242-9}}
-# {{cite journal | author=Anderson SL, Qiu J, and Rubin BY | title=Tocotrienols induce IKBKAP expression: a possible therapy for Familial Dysautonomia. | journal=Biochem. Biophys. Res. Commun. | year=2003 | pages=303-309 |volume=306 | id=PMID: 12788105}}
-# {{cite journal | author=Anderson SL, Rubin BY | title=Tocotrienols reverse IKAP and monoamine oxidase deficiencies in familial dysautonomia. | journal=Biochem. Biophys. Res. Commun | pages=150-156 | volume=336 | id=PMID: 16125677}}
-==Footnotes==
+==Further reading==
+* {{cite journal | author=Axelrod FB, Hilz MJ | title=Inherited autonomic neuropathies | journal=Semin Neurol | year=2003 | pages=381–90 | volume=23 | issue=4 | pmid=15088259 | doi=10.1055/s-2004-817722}}
-<div class="references-small"><references/></div>
+* {{cite journal | author=Axelrod FB | title=Familial dysautonomia | journal=Muscle Nerve | year=2004 | pages=352–63 | volume=29 | issue=3 | pmid=14981733 | doi=10.1002/mus.10499}}
-==See also==
-* [[Congenital insensitivity to pain]]
+* {{cite journal | author=Slaugenhaupt SA, Gusella JF | title=Familial dysautonomia | journal=Curr Opin Genet Dev | year=2002 | pages=307–11 | volume=12 | issue=3 | pmid=12076674 | doi=10.1016/S0959-437X(02)00303-9}}
-* [[Hereditary Sensory and Autonomic Neuropathy]]
+* {{cite journal | author=Felicia B Axelrod and Gabrielle Gold-von Simson | title=Hereditary sensory and autonomic neuropathies: types II, III, and IV | journal=Orphanet Journal of Rare Diseases | date=October 3, 2007 | volume=2 | issue=39 | pmid=17915006 | pmc=2098750 | doi=10.1186/1750-1172-2-39 | pages=39 }}
 ==External links==
+*[http://www.researchmatters.harvard.edu/medicine-health/articles/gene-familial-dysautonomia-discovered Gene for familial dysautonomia found]
+*{{WhoNamedIt|synd|3257|Riley-Day syndrome}}
+*{{Chorus|00356}}
+* [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=fd  GeneReviews/NCBI/NIH/UW entry on Familial Dysautonomia]
+==Support organizations==
+*[http://www.campsimcha.org Camp Simcha Special &mdash; a non-profit camp with special facilities for children with Familial Dysautonomia and other genetic conditions] (see [[Chai Lifeline]])
 *[http://www.curefd.org/ Cure FD Foundation; a non profit organization supporting research at Fordham University for a cure for Familial Dysautonomia]
 *[http://www.familialdysautonomia.org/ Dysautonomia Foundation, Inc.&mdash; a non-profit organization supporting medical research and treatment for those afflicted with Familial Dysautonomia]
 *[http://www.fdhope.org/ Familial Dysautonomia Hope Foundation]
+*[http://www.fdnow.org/ Familial Dysautonomia NOW FDNOW.org]
-*[http://www.researchmatters.harvard.edu/story.php?article_id=216 Gene for familial dysautonomia found]
 *[http://www.ndrf.org/ National Dysautonomia Research Foundation]
+*[http://www.kidsoc.org Kids of Courage &mdash; a non-profit organizing trips and camps with special facilities for children with Familial Dysautonomia] (see [[Kids of Courage]])
-*{{WhoNamedIt|synd|3257}}
-*{{Chorus|00356}}
+{{Autonomic diseases}}
+{{Factitial dermatitis}}
+{{Pain}}
+{{DEFAULTSORT:Familial Dysautonomia}}
-[[Category:Genetic disorders]]
-[[Category:Neurology]]
+[[Category:Autosomal recessive disorders]]
+[[Category:Neurocutaneous conditions]]
+[[category:Pain]]
+[[Category:Peripheral nervous system disorders]]
+<!--
-:he:דיסאוטונומיה משפחתית
+[[es:Disautonomía familiar]]
+[[it:Disautonomia familiare]]
+[[he:דיסאוטונומיה משפחתית]]
+[[pl:Rodzinna dysautonomia]]
+-->
 {{enWP|Familial dysautonomia}}

v·d·e Autonomic nervous system disorders]], Dysautonomia, autonomic- neuropathy (G90, 337)
HSAN	I · II · III/Familial dysautonomia · IV/Congenital insensitivity to pain with anhidrosis · V
Orthostatic intolerance	Postural orthostatic tachycardia syndrome · Orthostatic hypotension
Other	Horner's syndrome · Multiple system atrophy · Primary autonomic failure · Pure autonomic failure · Autonomic dysreflexia

v·d·e Factitial dermatitis (F45.8+L98.1, 306.3+698.4) and psychiatric and organic nervous system disease / neurodermatitis
F	Body dysmorphic disorder · Bromidrosiphobia · Delusional parasitosis · Dermatothlasia · Factitious dermatitis · Trichotillomania
G	Complex regional pain syndrome · Congenital insensitivity to pain with anhidrosis · Meralgia paraesthetica · Riley–Day syndrome · Sciatic nerve injury · Syringomyelia · Trigeminal neuralgia
K	Glossodynia
L	Malum perforans pedis · Neurotic excoriations · Factitial lymphedema
Ungrouped	Atypical chronic pain syndrome · Brachioradial pruritus · Notalgia paresthetica · Postencephalitic trophic ulcer · Psychogenic pruritus · Scalp dysesthesia · Scrotodynia/Vulvodynia · Traumatic neuroma · Trigeminal trophic lesion
Template:Integument navs

v·d·e Pain and nociception
Head and neck	Jaw and mouth (Odynophagia ) • Ear (otalgia, otitis media, otitis externa) • Eye (glaucoma) Head (headache, migraine, tension headache, cluster headache, cerebral aneurysm, sinusitis, meningitis) Neck (atypical myocardial infarction)
Thorax	Back (upper back, lower back, spinal disc herniation, degenerative disc disease, coccydynia) Breast (perimenstrual, breast cancer) • Chest (myocardial infarction, gastroesophageal reflux disease, pancreatitis, hiatus hernia, aortic dissection, asymptomatic pulmonary embolism, Tietze's syndrome) Shoulder (right side - cholecystitis)
Abdominal	Left and right upper quadrant (peptic ulcer disease, gastroenteritis, hepatitis, pancreatitis, cholecystitis, atypical myocardial infarction, abdominal aortic aneurysm, asymptomatic gastric cancer) • Left and right lower quadrant (appendicitis, ulcerative colitis, Crohn's disease, ectopic pregnancy, endometriosis, pelvic inflammatory disease, diverticulitis, urolithiasis, pyelonephritis, colorectal cancer)
Limbs	Arm (myocardial infarction, left arm) • Leg (deep vein thrombosis, peripheral artery occlusive disease, claudication, spinal disc herniation, sciatica)
Joints (arthralgia)	Small joints (osteoarthritis, rheumatoid arthritis, systemic lupus erythematosis, gout, pseudogout • Large joints (osteoarthritis, septic arthritis, hemarthrosis, osteonecrosis) • Back joints (ankylosing spondylitis, inflammatory bowel disease) • Other (psoriatic arthritis, Reiter's syndrome)
Musculoskeletal	Delayed onset muscle soreness, myalgia, physical trauma
Other/unspecified	cold pressor test, congenital insensitivity to pain, dolorimeter, HSAN (Type I, II congenital sensory neuropathy, III familial dysautonomia, IV congenital insensitivity to pain with anhidrosis, V congenital insensitivity to pain with partial anhidrosis), neuralgia, pain asymbolia, pain disorder, paroxysmal extreme pain disorder • Allodynia, breakthrough pain, chronic pain, hyperalgesia, hypoalgesia, hyperpathia, phantom pain, referred pain
Related concepts	Anterolateral system, gate control theory of pain, pain management (anesthesia, cordotomy), pain scale, pain threshold, pain tolerance, posteromarginal nucleus, substance P, suffering, OPQRST

Familial dysautonomia
Classification and external resources
Template:Px Facial features of a patient with familial dysautonomia over time. Note flattening of upper lip. By age 10 years prominence of lower jaw is apparent and by age 19 years there is mild erosion of right nostril due to inadvertent self-mutilation.
ICD-10	G 901
ICD-9	742.8
OMIM	223900
DiseasesDB	11631
eMedicine	oph/678
MeSH	D004402
GeneReviews	Template:Citation/make link