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| | {{Short description|A genetic disorder affecting multiple systems}} |
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| '''FG syndrome''' ('''FGS''') is a rare genetic syndrome caused by one or more recessive genes located on the [[X chromosome]] and causing physical anomalies and developmental delays. FG syndrome was named after the first letters of the surnames of the first patients noted with the disease.<ref name="Faq Pages">{{cite web|title=Faq Pages|url=http://www.fgsyndrome.org/faq/faq-features-of-fg-syndrome/faqs/26/|website=FG Syndrome Family Alliance|publisher=fgsyndrome.org|accessdate=20 September 2016}}</ref> First reported by American geneticists [[John M. Opitz]] and Elisabeth G. Kaveggia in 1974,<ref name=Opitz-1974/> its major clinical features include [[intellectual disability]], [[hyperactivity]], [[hypotonia]] (low muscle tone), and a characteristic facial appearance including [[macrocephaly]] (an abnormally large head).<ref name=Thompson/> | | '''FG syndrome''' is a rare [[genetic disorder]] that primarily affects [[males]]. It is characterized by a combination of physical, intellectual, and behavioral features. The syndrome is named after the initials of the first family described with the condition. |
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| ==Presentation==
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| FG syndrome's major clinical features include intellectual disability, usually severe; hyperactive behavior, often with an outgoing personality; severe constipation, with or without structural anomalies in the anus such as [[imperforate anus]]; [[macrocephaly]]; severe hypotonia; a characteristic facial appearance due to hypotonia, giving a droopy, "open-mouthed" expression, a thin upper lip, a full or pouting lower lip, and partial or complete loss of the [[corpus callosum]]. About a third of reported cases of individuals with FG syndrome die in infancy, usually due to respiratory infection; premature death is rare after infancy.<ref name=Thompson>{{cite journal |vauthors= Thompson E, Baraitser M |title= FG syndrome |journal= J Med Genet |volume=24 |issue=3 |pages=139–43 |year=1987 |pmid=3572995 |pmc=1049945 |doi=10.1136/jmg.24.3.139}}</ref>
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| ===Developmental effects===
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| Associated with agenesis (absence) of the corpus callosum, intellectual disabilities are common among individuals with FG syndrome.<ref name=Lyons>{{cite web|last1=Lyons|first1=M|title=MED12-Related Disorders|url=https://www.ncbi.nlm.nih.gov/books/NBK1676/|website=GeneReviews|accessdate=6 September 2016|publisher=University of Washington, Seattle|year=1993}}</ref> Motor ability is also impaired as a result of having FG syndrome and its effects on the development of neurons.<ref name=Lyons/> During infancy, problems arise in the gastrointestinal and gastroesophageal systems of the body.<ref name=Lyons/> The most common gastrointestinal problems include constipation from imperforated anuses and gastroesophageal reflux.<ref name=Lyons/> Cardiopulmonary defects also contribute to roughly 60% of premature deaths in infants with FG syndrome.<ref name=Lyons/> Of all of the congenital heart defects septal defects are the most common.<ref name=Lyons/> After infancy, long term survival has been recorded to individuals surviving beyond the age of 50.<ref name=Lyons/>
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| ==Genetics== | | ==Genetics== |
| Most mutations that cause FG syndrome can be found in the ''[[MED12]]'' gene. However, mutations have also been found in ''[[FMR1]]'', ''[[FLNA]]'', ''[[UPF3B]]'', ''[[CASK]]'', ''[[MECP2]]'' and ''[[ATRX]]'' genes.<ref name=Lyons/> Mutations on these different genes lead to the different types of FG syndrome, all with similar characteristics.<ref name=Lyons/> The FGS1 type mutation is the most common of the types, and is found in the ''MED12'' gene.<ref name=Lyons/>
| | FG syndrome is typically inherited in an [[X-linked recessive]] pattern, which means the gene associated with the condition is located on the [[X chromosome]]. Males, having only one X chromosome, are more frequently affected by X-linked disorders. The specific gene mutations associated with FG syndrome have been identified in several genes, including [[MED12]], which plays a role in [[transcriptional regulation]] and [[cell signaling]]. |
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| Known types and affected genes include:
| | ==Clinical Features== |
| | Individuals with FG syndrome often present with a distinctive set of clinical features, which may include: |
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| {| class="wikitable"
| | * '''[[Hypotonia]]''': Reduced muscle tone, which can lead to delayed motor skills. |
| |-
| | * '''[[Intellectual disability]]''': Ranging from mild to moderate, affecting cognitive development. |
| ! Type
| | * '''[[Behavioral problems]]''': Such as [[hyperactivity]], [[impulsivity]], and [[attention deficit disorder]]. |
| ! [[OMIM]]
| | * '''[[Macrocephaly]]''': An unusually large head size. |
| ! Gene
| | * '''[[Facial dysmorphism]]''': Distinctive facial features, including a prominent forehead, down-slanting [[palpebral fissures]], and a small chin. |
| ! Locus
| | * '''[[Constipation]]''': Chronic digestive issues are common. |
| |-
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| | FGS1
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| | {{OMIM2|305450}}
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| | ''[[MED12]]''
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| | Xq13
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| |-
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| | FGS2
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| | {{OMIM2|300321}}
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| | ''[[FLNA]]''
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| | Xq28
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| |-
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| | FGS3
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| | {{OMIM2|300406}}
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| | ''[[FGS3]]''
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| | Xp22.3
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| |-
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| | FGS4
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| | {{OMIM2|300422}}
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| | ''[[CASK]]''
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| | Xp11.4-p11.3
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| |-
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| | FGS5
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| | {{OMIM2|300581}}
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| | ''[[FGS5]]''
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| | Xq22.3
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| |}
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| ===''MED12'' gene===
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| The ''MED12'' gene codes for the mediator complex subunit 12 protein.<ref name="MED12 - Genetics Home Reference">{{cite web|url=https://ghr.nlm.nih.gov/gene/MED12#conditions|title=MED12 - Genetics Home Reference|last=|first=|date=|website=|publisher=U.S. National Library of Medicine|archive-url=|archive-date=|accessdate=6 September 2016}}</ref> The [[mediator complex]] is composed of around 25 different proteins that all help with the [[Regulation of gene expression|regulation]] of gene activity.<ref name="MED12 - Genetics Home Reference"/> This mediator complex regulates gene expression by bridging interaction between [[RNA polymerase II]] and gene-specific regulating proteins such as [[transcription factors]], [[repressor proteins]], [[activator proteins]], etc.<ref name="MED12 - Genetics Home Reference"/> Changes to this complex and the proteins associated can have a severe impact on the production of new proteins.<ref name="MED12 - Genetics Home Reference"/> The ''MED12'' gene is also thought to be highly linked to neuron development as well as high usage in the cells [[signal transduction]] pathway.<ref name="MED12 - Genetics Home Reference"/> This explains the slowed intellectual development individuals with FG syndrome have.<ref name="MED12 - Genetics Home Reference"/>
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| ==Diagnosis== | | ==Diagnosis== |
| {{Empty section|date=December 2017}}
| | The diagnosis of FG syndrome is based on clinical evaluation and the identification of characteristic features. Genetic testing can confirm the diagnosis by identifying mutations in the associated genes. A detailed family history is also important to assess the inheritance pattern. |
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| ==Treatment==
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| {{Empty section|date=December 2017}}
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| ==History==
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| [[File:Kim_Peek,_diagnosed_with_Savant_syndrome.jpg|thumb|upright|[[Kim Peek]] (1951–2009) probably had FG syndrome.]]
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| The name of the syndrome comes from the initials of the surnames of two sisters, who had five sons with the syndrome. The first study of the syndrome, published in 1974,<ref name=Opitz-1974>{{cite journal |vauthors= Opitz JM, Kaveggia EG |title= Studies of malformation syndromes of man XXXIII: the ''FG'' syndrome. An X-linked recessive syndrome of multiple congenital anomalies and mental retardation |journal= Z Kinderheilkd |volume=117 |issue=1 |pages=1–18 |year=1974 |doi=10.1007/BF00439020 |pmid=4365204|url= https://www.semanticscholar.org/paper/2bf5437c7bb03966789f7efaafcc5b126e20e0ea }}</ref> established that it was linked to inheritance of the [[X chromosome]].<ref name=Opitz-2008>{{cite journal |vauthors= Opitz JM, Smith JF, Santoro L |title= The FG syndromes (Online Mendelian Inheritance in Man 305450): perspective in 2008 |journal= Adv Pediatr |volume=55 |pages=123–70 |year=2008 |pmid=19048730 |doi=10.1016/j.yapd.2008.07.014}}</ref> | |
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| A 2008 study concluded that [[Kim Peek]], who was the basis for [[Dustin Hoffman|Dustin Hoffman's]] character Raymond Babbitt in the movie ''[[Rain Man]]'', probably had FG syndrome<ref name=Opitz-2008/> rather than [[autism]].
| | ==Management== |
| | There is no cure for FG syndrome, and treatment is symptomatic and supportive. Management strategies may include: |
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| ==See also==
| | * '''[[Physical therapy]]''': To improve muscle tone and motor skills. |
| *[[Lujan–Fryns syndrome]] | | * '''[[Occupational therapy]]''': To assist with daily living skills. |
| | * '''[[Speech therapy]]''': To address communication difficulties. |
| | * '''Behavioral interventions''': To manage hyperactivity and attention issues. |
| | * '''Educational support''': Tailored learning programs to accommodate intellectual disabilities. |
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| ==References== | | ==Prognosis== |
| {{reflist}}
| | The prognosis for individuals with FG syndrome varies depending on the severity of symptoms. With appropriate interventions and support, many individuals can lead fulfilling lives. Lifespan is typically not affected, although associated health issues may require ongoing management. |
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| == External links == | | ==Related pages== |
| {{Medical resources
| | * [[Genetic disorders]] |
| | DiseasesDB = 32162
| | * [[X-linked recessive inheritance]] |
| | ICD10 =
| | * [[Intellectual disability]] |
| | ICD9 =
| | * [[Behavioral disorders]] |
| | ICDO =
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| | OMIM = 305450
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| | MedlinePlus =
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| | eMedicineSubj =
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| | eMedicineTopic =
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| | eMedicine_mult =
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| | MeshID =
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| | GeneReviewsNBK = NBK1676
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| | GeneReviewsName = ''MED12''-related disorders
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| }}
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| {{Cytoskeletal defects}}
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| {{X-linked disorders}}
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| [[Category:X-linked recessive disorders]] | | [[Category:Genetic disorders]] |
| [[Category:Rare syndromes]] | | [[Category:Rare diseases]] |
| {{stub}}
| | [[Category:Syndromes]] |
A genetic disorder affecting multiple systems
FG syndrome is a rare genetic disorder that primarily affects males. It is characterized by a combination of physical, intellectual, and behavioral features. The syndrome is named after the initials of the first family described with the condition.
Genetics
FG syndrome is typically inherited in an X-linked recessive pattern, which means the gene associated with the condition is located on the X chromosome. Males, having only one X chromosome, are more frequently affected by X-linked disorders. The specific gene mutations associated with FG syndrome have been identified in several genes, including MED12, which plays a role in transcriptional regulation and cell signaling.
Clinical Features
Individuals with FG syndrome often present with a distinctive set of clinical features, which may include:
Diagnosis
The diagnosis of FG syndrome is based on clinical evaluation and the identification of characteristic features. Genetic testing can confirm the diagnosis by identifying mutations in the associated genes. A detailed family history is also important to assess the inheritance pattern.
Management
There is no cure for FG syndrome, and treatment is symptomatic and supportive. Management strategies may include:
- Physical therapy: To improve muscle tone and motor skills.
- Occupational therapy: To assist with daily living skills.
- Speech therapy: To address communication difficulties.
- Behavioral interventions: To manage hyperactivity and attention issues.
- Educational support: Tailored learning programs to accommodate intellectual disabilities.
Prognosis
The prognosis for individuals with FG syndrome varies depending on the severity of symptoms. With appropriate interventions and support, many individuals can lead fulfilling lives. Lifespan is typically not affected, although associated health issues may require ongoing management.
Related pages
