Coffin–Siris syndrome

Coffin–Siris syndrome
Synonyms	Dwarfism-Onychodysplasia, Fifth Digit Syndrome, Mental Retardation with Hypoplastic 5th Fingernails and Toenails, Short Stature-Onychodysplasia
Pronounce
Field
Symptoms
Complications
Onset
Duration
Types
Causes
Risks
Diagnosis
Differential diagnosis
Prevention
Treatment
Medication
Prognosis
Frequency
Deaths

Coffin–Siris Syndrome is a rare genetic disorder that causes developmental delays and absent fifth finger and toe nails. There had been 31 reported cases by 1991.<ref name="pmid1865473">,

 Coffin-Siris syndrome, 
 Journal of Medical Genetics, 
 
 Vol. 28(Issue: 5),
 pp. 338–41,
 DOI: 10.1136/jmg.28.5.338,
 PMID: 1865473,
 PMC: 1016855,</ref> The number of occurrences since then has grown and is now reported to be around 80.<ref>

metrowebukmetro. Twisted spine girl back playing football(link). {{{website}}}.

2008-10-13.

Accessed 13 June 2015.

</ref>

The differential includes Nicolaides–Baraitser syndrome.<ref name="pmid19606471">,

 Nicolaides-Baraitser syndrome: Delineation of the phenotype, 
 American Journal of Medical Genetics. Part A, 
 
 Vol. 149A(Issue: 8),
 pp. 1628–40,
 DOI: 10.1002/ajmg.a.32956,
 PMID: 19606471,</ref>

Presentation

• mild to severe intellectual disability,<ref>

Coffin-Siris syndrome(link). {{{website}}}.

8 June 2015.

Accessed 13 June 2015.

</ref><ref> Cha, Ariana Eunjung. NIH researchers sequence healthy volunteers' DNA and find they aren't so healthy after all(link). {{{website}}}.

4 June 2015.

Accessed 13 June 2015.

</ref> also called "developmental disability"<ref>

Greenville: A home of one's own - Ledger Transcript(link). {{{website}}}.

2015-05-14.

Accessed 13 June 2015.

</ref>

• short fifth digits with hypoplastic or absent nails
• low birth weight
• feeding difficulties upon birth
• frequent respiratory infections during infancy
• hypotonia
• joint laxity
• delayed bone age
• microcephaly
• coarse facial features, including wide nose, wide mouth, and thick eyebrows and lashes

Causes

Autosomal dominant inheritance is the most likely, usually by de novo mutation.

This syndrome has been associated with mutations in the ARID1B gene.<ref name=Vals2014>,

 Coffin-Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene, 
 European Journal of Human Genetics, 
 
 Vol. 22(Issue: 11),
 pp. 1327–9,
 DOI: 10.1038/ejhg.2014.25,
 PMID: 24569609,
 PMC: 4200437,</ref>

Mutations in SOX11 are associated to this syndrome.<ref name=pmid24886874>,

 De novo SOX11 mutations cause Coffin-Siris syndrome, 
 Nature Communications, 
 
 Vol. 5,
 pp. 4011,
 DOI: 10.1038/ncomms5011,
 PMID: 24886874,</ref>

A second gene that has been associated with this syndrome is the AT-rich interaction domain 2 (ARID2) gene.<ref name=Gazdagh2018>,

 Extending the clinical and genetic spectrum of ARID2 related intellectual disability. A case series of 7 patients, 
 European Journal of Medical Genetics, 
 
 Vol. 62(Issue: 1),
 pp. 27–34,
 DOI: 10.1016/j.ejmg.2018.04.014,
 PMID: 29698805,
 
 
 Full text,</ref>

The diagnosis is generally based on the presence of major and at least one minor clinical sign and can be confirmed by molecular genetic testing of the causative genes. Recent studies revealed that fifth finger nail/distal phalanx hypoplasia or aplasia is not a mandatory finding.

Treatment

There is no known cure or standard for treatment. Treatment is based on symptoms and may include physical, occupational and speech therapy and educational services as well.

External links

• Coffin–Siris syndrome on Orphanet
• synd/3426 at Who Named It?

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• 
  Diagram showing autosomal dominant inheritance
• 
  Boy with Coffin–Siris syndrome
• 
  Illustration of de novo mutations