View source for Medicine:Klippel–Feil syndrome

{{short description|Congenital condition characterised by fusion of two or more vertebrae in the neck}}
{{Infobox medical condition (new)
| name            = Klippel-Feil syndrome
| image           = Klippel–Feil syndrome.png
| image_size      = 300px
| alt             =
| caption         = Woman with Klippel–Feil syndrome
| pronounce       = {{IPAc-en|ˌ|k|l|ɪ|.|p|ə|l|_|ˈ|f|aɪ|l|}}
| synonyms        = Congenital dystrophia brevicollis, cervical vertebral fusion syndrome
| specialty       = Paediatrics, orthopaedics
| symptoms        = Cervical spine fusion, [[Medicine:Scoliosis|scoliosis]], [[Medicine:Spina bifida|spina bifida]], heart defect, respiratory problems, other syndromic features
| complications   =
| onset           = Congenital
| duration        =
| types           =
| causes          = Genetic mutations
| risks           = Family history
| diagnosis       =
| differential    =
| prevention      =
| treatment       =
| medication      =
| prognosis       = Shorter [[Biology:Life expectancy|life expectancy]] in some cases
| frequency       = 1 in 40,000 to 42,000 births, females more affected than males
| deaths          =
}}

'''Klippel–Feil syndrome''' ('''KFS'''), also known as '''cervical vertebral fusion syndrome''', is a [[Medicine:Rare disease|rare]] congenital condition characterized by the abnormal fusion of any two of the seven bones in the neck (cervical vertebrae).<ref>Andrews, James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. {{ISBN|0-7216-2921-0}}.</ref>{{Rp|578}} It results in a limited ability to move the neck and shortness of the neck, resulting in the appearance of a low hairline.<ref name=":1">{{Cite web|url=https://ghr.nlm.nih.gov/condition/klippel-feil-syndrome|title=Klippel-Feil syndrome|website=Genetics Home Reference|publisher=U.S. National Library of Medicine|language=en|access-date=2018-08-18}}</ref>

The syndrome is difficult to diagnose, as it occurs in a group of patients affected with many different abnormalities who can only be unified by the presence of fused or segmental cervical vertebrae.<ref>{{cite web |title=Klippel-Feil Syndrome |publisher=HONselect |url=http://www.hon.ch/HONselect/RareDiseases/EN/C05.116.099.370.535.html |access-date=2013-01-20 |archive-date=2018-06-12 |archive-url=https://web.archive.org/web/20180612141209/http://www.hon.ch/HONselect/RareDiseases/EN/C05.116.099.370.535.html |url-status=dead }}</ref> KFS is not always genetic and not always known about on the date of birth.

The disease was initially reported in 1884 by Maurice Klippel and André Feil from France.<ref>{{Cite journal|last1=Belykh|first1=Evgenii|last2=Malik|first2=Kashif|last3=Simoneau|first3=Isabelle|last4=Yagmurlu|first4=Kaan|last5=Lei|first5=Ting|last6=Cavalcanti|first6=Daniel D.|last7=Byvaltsev|first7=Vadim A.|last8=Theodore|first8=Nicholas|last9=Preul|first9=Mark C.|date=July 2016|title=Monsters and the case of L. Joseph: André Feil's thesis on the origin of the Klippel-Feil syndrome and a social transformation of medicine|journal=Neurosurgical Focus|volume=41|issue=1|pages=E3|doi=10.3171/2016.3.FOCUS15488|issn=1092-0684|pmid=27364256|doi-access=free}}</ref> In 1919, in his [[Social:Doctor of Philosophy|Doctor of Philosophy]] [[Thesis|thesis]],<ref>{{cite journal|author=Feil A|title=These de medicine, Paris. L'absence et la diminution des vertèbres cervicales (étude clinique et pathogénique); le syndrome de réduction numérique cervicales. | year=1919}}</ref> André Feil suggested another classification of the syndrome, encompassing not only deformation of the cervical spine, but also deformation of the lumbar and thoracic spine.

==Signs and symptoms==
[[File:Klippel–Feil syndrome and Sprengel's deformity.png|thumb|upright=1.25|[[CT scan|CT scan]] showing fused cervical vertebrae and Sprengel's deformity (arrow), as seen in Klippel–Feil syndrome]]

KFS is associated with many other abnormalities of the body, hence thorough evaluation of all patients with fused cervical vertebrae at birth is required. Furthermore, it is unclear whether KFS is a unique disease, or if it is one part of a spectrum of congenital spinal deformities.{{citation needed|date=October 2020}}

KFS is usually diagnosed after birth. The most common signs of the disorder are restricted mobility of the neck and upper spine and a shortened neck with the appearance of a low hairline at the back of the head.{{citation needed|date=October 2020}}

Associated abnormalities may include:<ref name=":0">{{Cite journal|last=Paradowska, Szeląg, Sławecki|date=2007|title=Klippel−Feil Syndrome – Review of the Literature|url=http://www.dmp.am.wroc.pl/artykuly/DMP_2007444491.pdf|url-status=dead|journal=Dent. Med. Probl.|archive-url=https://web.archive.org/web/20151001052200/http://www.dmp.am.wroc.pl/artykuly/DMP_2007444491.pdf|archive-date=2015-10-01|access-date=2015-09-30}}</ref><ref>{{Cite journal|title = Dental team management for a patient with Klippel-Feil syndrome: case report|journal = Special Care in Dentistry|date = 2009-12-01|issn = 1754-4505|pmid = 19886936|pages = 244–248|volume = 29|issue = 6|doi = 10.1111/j.1754-4505.2009.00101.x|first1 = Marina de Deus Moura|last1 = de Lima|first2 = Karem Lopez|last2 = Ortega|first3 = Luis Carlos Arias|last3 = Araújo|first4 = Marcelo Melo|last4 = Soares|first5 = Marina Helena Cury Gallottini|last5 = de Magalhães}}</ref><ref>{{cite book|last1=Marchiori|first1=Dennis|title=Clinical Imaging - E-Book: With Skeletal, Chest and Abdomen Pattern Differentials|date=2004|publisher=Elsevier Health Sciences|isbn=978-0323071277|url=https://books.google.com/books?id=Iw_xAT0BqcIC&q=Srb%27s+anomaly|access-date=25 January 2018|language=en}}</ref><ref>{{cite journal |vauthors=Farsetti P, Weinstein SL, Caterini R, De Maio F, Ippolito E |title=Sprengel's deformity: long-term follow-up study of 22 cases |journal=J Pediatr Orthop B |volume=12 |issue=3 |pages=202–10 |date=May 2003 |pmid=12703036 |doi= 10.1097/01202412-200305000-00007}}
{{cite book |editor-last=Sarwark |editor-first=JF |editor2-last=LaBella |editor2-first=CR |title=Pediatric Orthopaedics and Sports Injuries: A Quick Reference Guide |publisher=American Academy of Pediatrics |location=Elk Grove Village IL |year=2010 |pages=231–4 }}
</ref>
* [[Medicine:Scoliosis|Scoliosis]] (sideways curvature of the spine)
* [[Medicine:Spina bifida|Spina bifida]]
* Problems with the kidneys and the [[Biology:Rib|rib]]s
* Cleft palate
* Dental problems (delayed [[Biology:Dentition|dentition]], cavities, missing teeth)
* Respiratory problems
* Heart defects
* Short stature
* [[Medicine:Duane syndrome|Duane syndrome]]
* [[Medicine:Srb's anomaly|Srb's anomaly]]
* Sprengel's deformity

The disorder also may be associated with abnormalities of the head and face, [[Biology:Skeleton|skeleton]], sex organs, [[Biology:Muscle|muscle]]s, [[Biology:Brain|brain]] and [[Biology:Spinal cord|spinal cord]], arms, legs and fingers.{{citation needed|date=November 2020}}

==Genetics==
[[Biology:Mutation|Mutation]]s of the ''[[Biology:GDF6|GDF6]]'', ''[[Biology:GDF3|GDF3]]'' and ''MEOX1'' gene are associated with KFS.<ref name=":1" /> The cause of the condition is unknown in individuals with KFS who do not have mutations of these two genes. ''GDF6'' and ''GDF3'' provide the body with instructions for making proteins involved in regulating the growth and maturation of bone and cartilage. ''GDF6'' specifically is involved in the formation of vertebral bones, among others, and establishing boundaries between bones in skeletal development. ''GDF3'' is involved with bone and cartilage growth. Mutations of ''GDF6,'' ''GDF3'' and ''MEOX1'' cause a reduced number of functional proteins that are coded by these genes, but it is unclear exactly how a shortage in these proteins leads to incomplete separation of the vertebrae in people with KFS.<ref name="ghr.nlm.nih.gov"/> However, when the ''GDF6'' gene was removed in mice, the result was the fusion of bones.<ref>{{cite journal |vauthors=Tassabehji M, Fang ZM, Hilton EN, etal |title=Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome |journal=Hum. Mutat. |volume=29 |issue=8 |pages=1017–27 |date=August 2008 |pmid=18425797 |doi=10.1002/humu.20741 |s2cid=5276691 |doi-access=free }}</ref>

These mutations can be inherited in two ways:
* [[Biology:Dominance (genetics)|Autosomal dominant inheritance]], where one copy of the altered gene in each cell is sufficient to cause the disorder, is especially associated with C2-C3 fusion.<ref name="ghr.nlm.nih.gov"/>
* Autosomal recessive inheritance, where both copies of a gene contain mutations, is especially associated with C5-C6 fusion.<ref name="ghr.nlm.nih.gov"/>
* Another autosomal dominant form (mapped on locus ''8q22.2''), known as KFS with laryngeal malformation, has been identified. It is also known as segmentation syndrome 1.<ref>{{OMIM|118100|Klippel-Feil Syndrome 1, Autosomal Dominant; KFS1}}</ref><ref>{{Cite web | url=http://rarediseases.info.nih.gov/GARD/Disease.aspx?diseaseID=6838 | title=Segmentation syndrome 1 &#124; Genetic and Rare Diseases Information Center (GARD) – an NCATS Program | access-date=2009-06-13 | archive-date=2012-05-31 | archive-url=https://web.archive.org/web/20120531191627/http://rarediseases.info.nih.gov/GARD/Disease.aspx?diseaseID=6838 | url-status=dead }}</ref>

==Diagnosis==
The heterogeneity of KFS has made it difficult to outline the [[Medicine:Diagnosis|diagnosis]] as well as the [[Medicine:Prognosis|prognosis]] for this disease.{{citation needed|date=October 2020}}

===Classification===
In 1912, Maurice Klippel and Andre Feil independently provided the first descriptions of KFS. They described patients who had a short, webbed neck; decreased range of motion (ROM) in the cervical spine; and a low hairline. Feil subsequently classified the syndrome into three categories:{{citation needed|date=December 2020}}
* Type I—Fusion of C2 and C3 with occipitalization of the atlas. In 1953, further complications were later reported by McRae; flexion and extension is concentrated within the C1 and C2 vertebrae. As with aging, the odontoid process can become hypermobile, narrowing the space where the [[Biology:Spinal cord|spinal cord]] and brain stem travel ([[Medicine:Spinal stenosis|spinal stenosis]]).
* Type II—Long fusion below C2 with an abnormal occipital-cervical junction. Similar to the C2-C3 fusion of McRae and could be viewed as a more elaborate variation. Flexion, extension, and rotation are all concentrated in the area of an abnormal odontoid process or poorly developed ring of C1 which cannot withstand the effects of aging.
* Type III—A single open interspace between two fused segments. Cervical spine motion is concentrated at single open articulation. This [[Medicine:Hypermobility (joints)|hypermobility]] may lead to instability or degenerative [[Medicine:Osteoarthritis|osteoarthritis]]. This pattern can be recognized as the cervical spine is often seen to be at an angle or hinge at this open segment.

A classification scheme for KFS was proposed in 1919 by Andre Feil, which accounted for [[Medicine:Neck|cervical]], thoracic, and [[Biology:Lumbar|lumbar]] spine malformations.<ref>Feil A. L'absence et la diminuaton des vertebres cervicales (etude cliniqueet pathogenique); le syndrome dereduction numerique cervicales. Theses de Paris; 1919.</ref>

However, in 2006, Dino Samartzis and colleagues proposed three classification-types that specifically addressed the cervical spine anomalies and their associated cervical spine-related symptoms, with additional elaboration on various time-dependent factors regarding this syndrome.<ref>
{{cite journal |vauthors=Samartzis DD, Herman J, Lubicky JP, Shen FH |title=Classification of congenitally fused cervical patterns in Klippel-Feil patients: epidemiology and role in the development of cervical spine-related symptoms |journal=Spine |volume=31 |issue=21 |pages=E798–804 |year=2006 |pmid=17023841 |doi=10.1097/01.brs.0000239222.36505.46 |s2cid=19744236 }}</ref>

==Treatment==
<!-- Deleted image removed: [[File:Exposure of the Cervical Vertebrae.jpg|thumb|right|Exposed vertebrae during cervical spinal fusion surgery.]] -->
Treatment for KFS is symptomatic and may include surgery to relieve cervical or [[Medicine:Craniocervical instability|craniocervical instability]] and constriction of the spinal cord, and to correct [[Medicine:Scoliosis|scoliosis]].{{Citation needed|date=April 2010}}

If symptomatic treatment fails, spinal surgery may provide relief. Adjacent segment disease and scoliosis are two examples of common symptoms associated with Klippel–Feil syndrome, and they may be treated surgically. The three categories treated for types of spinal cord deficiencies are massive fusion of the cervical spine (Type I), the fusion of 1 or 2 vertebrae (Type II), and the presence of thoracic and lumbar spine anomalies in association with type I or type II Klippel–Feil syndrome (Type III).{{citation needed|date=October 2020}}

Adjacent segment disease can be addressed by performing cervical disc arthroplasty using a device such as the Bryan cervical disc prosthesis.<ref>{{cite journal |vauthors=Goffin J, Casey A, Kehr P, etal |title=Preliminary clinical experience with the Bryan Cervical Disc Prosthesis |journal=Neurosurgery |volume=51 |issue=3 |pages=840–5; discussion 845–7 |date=September 2002 |pmid=12188968 |doi=10.1227/00006123-200209000-00048|s2cid=41447240 |url=https://lirias.kuleuven.be/handle/123456789/17531 }}</ref> The option of the surgery is to maintain range of motion and attenuate the rate of adjacent segment disease advancement without fusion.<ref>{{cite journal |vauthors=Papanastassiou ID, Baaj AA, Dakwar E, Eleraky M, Vrionis FD |title=Failure of cervical arthroplasty in a patient with adjacent segment disease associated with Klippel-Feil syndrome |journal=Indian J Orthop |volume=45 |issue=2 |pages=174–7 |date=March 2011 |pmid=21430874 |pmc=3051126 |doi=10.4103/0019-5413.77139 |doi-access=free }}</ref> Another type of arthroplasty that is becoming an alternate choice to [[Medicine:Spinal fusion|spinal fusion]] is Total Disc Replacement. Total disc replacement objective is to reduce pain or eradicate it.<ref>{{cite journal |vauthors=Phillips FM, Garfin SR |title=Cervical disc replacement |journal=Spine |volume=30 |issue=17 Suppl |pages=S27–33 |date=September 2005 |pmid=16138062 |doi=10.1097/01.brs.0000175192.55139.69|s2cid=46420208 |doi-access=free }}</ref> [[Medicine:Spinal fusion|Spinal fusion]] is commonly used to correct spinal deformities such as [[Medicine:Scoliosis|scoliosis]]. [[Medicine:Arthrodesis|Arthrodesis]] is the last resort in pain relieving procedures, usually when arthroplasties fail.{{citation needed|date=November 2020}}

==Prognosis==
The [[Medicine:Prognosis|prognosis]] for most individuals with KFS is good if the disorder is treated early and appropriately. Activities that can injure the neck should be avoided, as it may contribute to further damage. Other diseases associated with the syndrome can be fatal if not treated, or if found too late to be treatable.<ref name="CartwrightWallace2007">{{cite book|url=https://books.google.com/books?id=G6o3uSlfRKcC&pg=PA205|title=Nursing care of the pediatric neurosurgery patient|author1=Cathy C. Cartwright|author2=Donna C. Wallace|date=3 May 2007|isbn=978-3-540-29703-1|pages=205–|publisher=Springer |access-date=25 December 2010}}</ref>

In less than 30% of cases, individuals with KFS will present with heart defects.<ref>{{Cite web | url=https://rarediseases.info.nih.gov/diseases/10280/klippel-feil-syndrome | title=Klippel Feil syndrome - About the Disease - Genetic and Rare Diseases Information Center | access-date=2020-10-15 | archive-date=2021-04-11 | archive-url=https://web.archive.org/web/20210411150809/https://rarediseases.info.nih.gov/diseases/10280/klippel-feil-syndrome | url-status=dead }}</ref> If these heart defects are present, they often lead to a shortened [[Biology:Life expectancy|life expectancy]], the average being 35–45 years of age among males and 40–50 among females. This condition is similar to the heart failure seen in [[Biography:Gigantism|gigantism]].<ref>{{cite journal|vauthors=McGaughran JM, Kuna P, Das V|date=October 1998|title=Audiological abnormalities in the Klippel-Feil syndrome|journal=Arch. Dis. Child.|volume=79|issue=4|pages=352–5|doi=10.1136/adc.79.4.352|pmc=1717726|pmid=9875048}}</ref>

==Epidemiology==
The [[Prevalence|prevalence]] of KFS is unknown due to the lack of studies to determine its prevalence.<ref>Angeli, E., Wagner, J., Lawrick, E., Moore, K., Anderson, M., Soderland, L., & Brizee, A. (2010, May 5). General format title. Retrieved from http://owl.english.purdue.edu/owl/resource/560/01/</ref> It is estimated to occur 1 in 40,000 to 42,000 newborns worldwide. In addition, females seem to be affected slightly more often than males.<ref name="ghr.nlm.nih.gov">{{NLM|klippel-feil-syndrome|}}</ref>

==Notable cases==
=== Ancient ===
* A case of a child in {{wipe|Switzerland}} was discovered in a necropolis dated between 4500 and 4000 BC.<ref>{{Cite web | url=http://www.klippel-feil.info/histoire.html | title=Aspects historiques}}</ref>
* In 2009, archaeologists excavating at a [[History:Neolithic|Neolithic]] site of the Đa Bút culture of northern Vietnam discovered the remains of a young man around age 25, "Burial 9", living between 2000 BC and 1500 BC with Klippel–Feil syndrome, who had apparently been supported by his subsistence-level community for at least a decade before his death.<ref>{{cite web|url=http://dsc.discovery.com/news/2009/08/06/paralyzed-human.html |title=Oldest Known Paralyzed Human Discovered |access-date=2014-01-18 |url-status=bot: unknown |archive-url=https://archive.today/20120710173417/http://dsc.discovery.com/news/2009/08/06/paralyzed-human.html |archive-date=2012-07-10 }}</ref><ref>{{cite journal|last1=Tilley|first1=Lorna|last2=Oxenham|first2=Marc F|title=Survival against the odds: Modeling the social implications of care provision to seriously disabled individuals|journal=International Journal of Paleopathology|date=March 2011|volume=1|issue=1|pages=35–42|doi=10.1016/j.ijpp.2011.02.003|pmid=29539340|hdl=1885/54871|hdl-access=free}}</ref><ref>{{cite news|last1=Gorman|first1=James|title=Ancient Bones That Tell a Story of Compassion|url=https://www.nytimes.com/2012/12/18/science/ancient-bones-that-tell-a-story-of-compassion.html|access-date=12 April 2015|agency=The New York Times|issue=17 December 2012, New York edition, D1|work=The New York Times|date=2012-12-17}}</ref>
* The 18th Dynasty Egyptian pharaoh Tutankhamun is believed by some to have had Klippel–Feil syndrome,<ref>{{cite news |url=https://www.telegraph.co.uk/news/worldnews/africaandindianocean/egypt/1408698/Tutankhamun-shows-his-face-80-years-after-tomb-is-opened.html |title=Tutankhamun shows his face 80 years after tomb is opened |work=The Telegraph |location=London|access-date=2007-07-12 |date=2002-09-29 |last1=Barrow |first1=Becky }}</ref> though others dispute this claim.<ref>{{cite journal |vauthors=Boyer RS, Rodin EA, Grey TC, Connolly RC |title=The skull and cervical spine radiographs of Tutankhamen: a critical appraisal |journal=AJNR. American Journal of Neuroradiology |volume=24 |issue=6 |pages=1142–7 |year=2003 |pmid=12812942 |pmc=8149017 |url=http://www.ajnr.org/cgi/content/full/24/6/1142}}</ref>

=== Contemporary ===
* English cricketer Gladstone Small<ref>{{cite news|last=Hughes|first=Simon|url=http://content-www.cricinfo.com/ci/content/story/74180.html|title=Small gains from wealth of partners|work=Cricinfo|date=1997-09-05|access-date=2007-12-13}}</ref>
* "Big" Ed Brown from the TLC series, ''90 Day Fiancé''.
* Kansas City Chiefs wide receiver Justyn Ross.

==References==
{{Reflist}}
''This article incorporates information in the public domain prepared by the [http://www.ninds.nih.gov/ National Institute of Neurological Disorders and Stroke].''

== External links ==
* {{curlie|Health/Conditions_and_Diseases/Musculoskeletal_Disorders/Congenital_Anomalies/Klippel-Feil_Syndrome/}}
{{Medical resources
|   DiseasesDB     = 7197
|   ICD10          = {{ICD10|Q|76|1|q|65}}
|   ICD9           = {{ICD9|756.16}}
|   ICDO           =
|   OMIM           = 118100
|   OMIM_mult      = {{OMIM|214300||none}}
|   MedlinePlus    =
|   eMedicineSubj  = orthoped
|   eMedicineTopic = 408
|   MeshID         = D007714
}}



{{DEFAULTSORT:Klippel-Feil syndrome}}
[[Category:Genodermatoses]]
[[Category:Rare syndromes]]

{{Sourceattribution|Klippel–Feil syndrome}}