Björnstad syndrome का स्रोत देखें

{{Infobox medical condition (new)
| name          = Björnstad syndrome
| synonyms      = BJS, Deafness and pili torti (Bjornstad type), Pili torti and nerve deafness, Pili-torti deafness syndrome, Pili torti-sensorineural hearing loss, PTD<ref>{{cite web |title=OMIM Entry - # 262000 - Bjornstad Syndrome; BJS |url=https://omim.org/entry/262000 |website=omim.org |accessdate=8 April 2019 |language=en-us}}</ref>
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| symptoms      = Pili torti, hearing loss, alopecia, mental retardation
| complications = 
| onset         = Infancy or early childhood
| duration      = 
| types         = 
| causes        = Mutation of BCS1L
| risks         = 
| diagnosis     = 
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| frequency     = Extremely rare - less than 50 documented cases
| deaths        = 
}}
[[File:Autosomal recessive - mini.svg|thumb|Björnstad syndrome is inherited in an autosomal recessive pattern.]]
[[File:Menkes disease3.jpg|thumb|Microscopic image of pili torti]]
'''Björnstad syndrome''' is an autosomal recessive [[congenital]] condition involving [[pili torti]], sensorineural [[deafness]], and hair abnormalities.<ref name=":3">{{cite journal|last1=Siddiqi|first1=Saima|last2=Siddiq|first2=Saadat|last3=Mansoor|first3=Atika|last4=Jaap|first4=Oostrik|last5=Nafees|first5=Ahmad|last6=Syed Ali|first6=Raza Kazmi|last7=Hannie|first7=Kremer|last8=Raheel|first8=Qamar|last9=Margit|first9=Schraders|date=December 1, 2013|title=Novel mutation in AAA domain of BCS1L causing Bjornstad syndrome|journal=Journal of Human Genetics|volume=12|issue=58|pages=819–820|doi=10.1038/jhg.2013.101|pmid=24172246|doi-access=free}}</ref> It was first characterized in 1965, in Oslo, by prof. Roar Theodor Bjørnstad after he observed an association between pili torti and hearing loss.<ref>Bjornstad, R. Pili torti and sensory-neural loss of hearing. Proc. 7th Meeting Northern Derm. Soc., Copenhagen May-29, 1965.</ref> The condition is extremely rare, with less than 50 cases documented in medical literature worldwide.<ref name=":0" />

Björnstad syndrome is caused by mutations of the [[BCS1L]] gene. The protein product of this gene is BCS1L, which plays an important role in oxidative phosphorylation.<ref name="pmid17314340">{{cite journal |vauthors=Hinson JT, Fantin VR, Schönberger J |title=Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome |journal=N. Engl. J. Med. |volume=356 |issue=8 |pages=809–19 |date=February 2007 |pmid=17314340 |doi=10.1056/NEJMoa055262 |display-authors=etal}}</ref> Mutated BCS1L increases production of reactive oxygen species, which may be the molecular cause of pili torti and hearing loss, both of which are associated with Björnstad syndrome.<ref name="pmid17314340" /> Pili torti is recognized in early childhood and is characterized by twisted hair shafts and brittle hair.<ref>{{cite journal|last1=Hinson|first1=J. Travis|last2=Fantin|first2=Valeria R.|last3=Schönberger|first3=Jost|last4=Breivik|first4=Noralv|last5=Siem|first5=Geir|last6=McDonough|first6=Barbara|last7=Sharma|first7=Pankaj|last8=Keogh|first8=Ivan|last9=Godinho|first9=Ricardo|last10=Santos|first10=Felipe|last11=Esparza|first11=Alfonso|last12=Nicolau|first12=Yamileth|last13=Selvaag|first13=Edgar|last14=Cohen|first14=Bruce H.|last15=Hoppel|first15=Charles L.|last16=Tranebjærg|first16=Lisbeth|last17=Eavey|first17=Roland D.|last18=Seidman|first18=J.G.|last19=Seidman|first19=Christine E.|title=Missense Mutations in the BCS1L Gene as a Cause of the Björnstad Syndrome|journal=New England Journal of Medicine|date=22 February 2007|volume=356|issue=8|pages=809–819|doi=10.1056/NEJMoa055262|issn=0028-4793|pmid=17314340}}</ref> The hearing loss usually becomes evident very early in life as well, often in the first year.

== Signs and symptoms ==
The two major symptoms of Björnstad syndrome are [[pili torti]] and sensorineural hearing impairment.<ref>{{Cite web|title=Björnstad syndrome: MedlinePlus Genetics|url=https://medlineplus.gov/genetics/condition/bjornstad-syndrome/|access-date=2021-04-26|website=medlineplus.gov|language=en}}</ref> These two symptoms typically appear before the age of 2 and are present in 80-99% of individuals with Björnstad syndrome.<ref name=":0">{{Cite web|title=Bjornstad syndrome {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|url=https://rarediseases.info.nih.gov/diseases/22/bjornstad-syndrome|access-date=2021-04-26|website=rarediseases.info.nih.gov}}</ref> Approximately 5-29% of individuals also experience intellectual disabilities and [[hypogonadism]].<ref name=":0" /> Cases showing lack of hair pigmentation and [[anhidrosis]] have also been documented.<ref name=":0" />

Pili torti is a hair abnormality characterized by twisted hair shafts. In Björnstad syndrome patients, the hair usually appears dry, fragile, coarse, and is easily broken.<ref name=":0" /> In some patients, hair abnormalities only affect hair on the head, although cases affecting eyebrows, eyelashes, and hair on other parts of the body have been documented. Weakening of the hair associated with pili torti also causes [[Hair loss|alopecia]] in approximately 80% of patients.<ref name=":0" />

The severity of hearing loss associated with Björnstad syndrome varies. Some individuals are unable to hear sounds at certain frequencies, while others are completely deaf. Their hearing loss is caused by tissue damage of the inner ear.<ref name=":2">{{Cite web|title=OMIM Entry - # 262000 - BJORNSTAD SYNDROME; BJS|url=https://www.omim.org/entry/262000#5|access-date=2021-04-26|website=www.omim.org}}</ref>

== Diagnosis ==
Roar Theodor Björnstad first noticed a correlation between pilli torti and hearing loss in 1965, and subsequently diagnosed eight patients with Björnstad syndrome. Out of these eight patients with pili torti, five experienced sensorineural deafness.<ref name=":1">{{Cite journal|last=Selvaag|first=E.|date=2000-02-23|title=Pili torti and sensorineural hearing loss. A follow-up of Bjørnstad’s original patients and a review of the literature|url=https://www.jle.com/en/revues/ejd/e-docs/pili_torti_and_sensorineural_hearing_loss._a_follow_up_of_bj_rnstads_original_patients_and_a_review_of_the_literature_100744/article.phtml|journal=European Journal of Dermatology|volume=10|issue=2|issn=1167-1122}}</ref> Björnstad presented his diagnosis and observations at a medical conference in Copenhagen.<ref name=":1" /> 

Björnstad syndrome is diagnosed by observation of twisted hair, known as pili torti, which can be observed as early as birth. To confirm presence of pili torti, the hair shafts of an individual are examined under an [[electron microscope]]. Any infants with confirmed pili torti should undergo a series of auditory tests to evaluate potential sensorineural deafness. Finally, a diagnosis of Björnstad syndrome can be confirmed by genetic testing for mutations in the BCS1L gene.<ref>{{Cite web|title=Björnstad Syndrome|url=https://rarediseases.org/rare-diseases/bjornstad-syndrome/|access-date=2021-04-27|website=NORD (National Organization for Rare Disorders)|language=en-US}}</ref>

== Genetics ==
Björnstad syndrome is caused by a mutation in the BCS1L gene (position [[Chromosome 2|2pq35]]) and is inherited in an [[Autosomal Recessive|autosomal recessive]] pattern. BCS1L is a protein that adds Rieske Fe/S to [[complex III]] during [[oxidative phosphorylation]] of [[cellular respiration]]. Mutations of BCS1L gene prevents the protein product from aiding in complex III formation, which reduces oxidative phosphorylation and increases the production of reactive oxygen species.<ref name="pmid17314340" /> 

Two [[Missense mutation|missense mutations]] linked to Björnstad syndrome have been documented, but several other variants are suspected to be pathogenic.<ref>{{Cite web|title=603647[MIM]). - ClinVar - NCBI|url=https://www.ncbi.nlm.nih.gov/clinvar?term=603647%5BMIM%5D).|access-date=2021-04-27|website=www.ncbi.nlm.nih.gov}}</ref> The clinical severity of different BCS1L mutations may be caused by the varying production of reactive oxygen species.<ref name="pmid17314340" /> The symptoms of Björnstad syndrome may be attributed to a particular sensitivity of inner ear and hair tissues to reactive oxygen species, but more research is needed.<ref name=":2" /> Mutations of the BCS1L gene may also result in [[GRACILE syndrome]], which is an inherited lethal metabolic disease.<ref name=":0" />

== Epidemiology ==
Björnstad syndrome is extremely rare, with less than 50 documented cases worldwide.<ref name=":0" /> In 2013, five individuals from a [[Consanguinity|consanguineous]] Pakistani family were diagnosed with Björnstad syndrome. They each experienced a varying degree of progressive hearing loss as well as hair loss on the scalp. The males with Björnstad syndrome also experienced shorter stature.<ref name=":3" />

Given its autosomal recessive inheritance pattern, Björnstad syndrome should theoretically affect males and females in equal numbers. However, more females than males have been diagnosed with Björnstad syndrome in medical literature.<ref name=":4">{{cite web|title=Bjornstad syndrome|url=https://rarediseases.info.nih.gov/diseases/22/bjornstad-syndrome|website=NCATS|publisher=Genetic and rare diseases information center|accessdate=17 April 2018}}</ref>

== See also ==
*[[GRACILE syndrome]]
*[[Mitochondrial complex II deficiency|Mitochondrial complex III deficiency]]

==References==
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== External links ==
{{Medical resources
| DiseasesDB      = 33516
| ICD10           = 
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| OMIM            = 262000
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| Orphanet        = 123
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{{Congenital malformations and deformations of skin appendages}}
{{Disorders of TCA and ETC}}

{{DEFAULTSORT:Bjornstad syndrome}}
[[Category:TCA and ETC metabolism disorders]]
[[Category:Syndromes affecting hearing]]
[[Category:Rare syndromes]]