Coffin-Siris syndrome

Title

Other Names:

Fifth digit syndrome; Intellectual disability with absent fifth fingernail and terminal phalanx

Categories:

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

Summary Summary

Coffin-Siris syndrome is a genetic condition that causes variable degrees of learning disability, developmental delays, underdeveloped “pinky” toenails or fingernails, and distinct facial features. It can be caused by a change (mutation) in any of several genes including the ARID1A, ARID1B, SMARCA4, SMARCB1, or SMARCE1 genes. Coffin-Siris syndrome follows an autosomal dominant pattern of inheritance, however it usually occurs for the first time in a family due to a new mutation.^[1] Occupational, physical, and/or speech therapy can help affected individuals reach their full potential.^[2]

Last updated: 1/5/2016

Symptoms Symptoms

The signs and symptoms of Coffin-Siris syndrome vary. More commonly described symptoms include:^[1]

Mild to severe intellectual disability
Mild to severe speech delay
Mild to severe delay in motor skills, such as sitting and walking
Underdeveloped fingertips or toes
Missing “pinky” fingernails or toenails
Distinctive facial features, such as a wide mouth, thick lips, thick eyelashes and brows, wide nose, and flat nasal bridge
Extra hair growth on the face and body
Sparse scalp hair

Other symptoms that have been described in infants and children with Coffin-Siris syndrome include:^[1]

Small head size
Frequent respiratory infections in infancy
Feeding difficulty in infancy
Failure to thrive
Short stature
Low muscle tone
Loose joints
Eye abnormalities
Heart abnormalities
Brain abnormalities
Kidney abnormalities

Last updated: 1/5/2016

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of the dentition	Very frequent (present in 80%-99% of cases)
Aplasia/Hypoplasia of the distal phalanx of the 5th finger	Very frequent (present in 80%-99% of cases)
Coarse facial features	Very frequent (present in 80%-99% of cases)
Feeding difficulties in infancy	Very frequent (present in 80%-99% of cases)
Generalized hirsutism	Very frequent (present in 80%-99% of cases)
Hypoplastic fifth fingernail	Very frequent (present in 80%-99% of cases)
Intellectual disability	Very frequent (present in 80%-99% of cases)
Long eyelashes	Very frequent (present in 80%-99% of cases)
Microcephaly	Very frequent (present in 80%-99% of cases)
Muscular hypotonia	Very frequent (present in 80%-99% of cases)
Short distal phalanx of finger	Very frequent (present in 80%-99% of cases)
Slow-growing hair	Very frequent (present in 80%-99% of cases)
Thick eyebrow	Very frequent (present in 80%-99% of cases)
Thick lower lip vermilion	Very frequent (present in 80%-99% of cases)
Wide nasal bridge	Very frequent (present in 80%-99% of cases)
Abnormality of cardiovascular system morphology	Frequent (present in 30%-79% of cases)
Aplasia/Hypoplasia of the cerebellum	Frequent (present in 30%-79% of cases)
Aplasia/Hypoplasia of the patella	Frequent (present in 30%-79% of cases)
Cryptorchidism	Frequent (present in 30%-79% of cases)
Dandy-Walker malformation	Frequent (present in 30%-79% of cases)
Depressed nasal ridge	Frequent (present in 30%-79% of cases)
Elbow dislocation	Frequent (present in 30%-79% of cases)
Hearing impairment	Frequent (present in 30%-79% of cases)
Intrauterine growth retardation	Frequent (present in 30%-79% of cases)
Joint hyperflexibility	Frequent (present in 30%-79% of cases)
Nystagmus	Frequent (present in 30%-79% of cases)
Recurrent respiratory infections	Frequent (present in 30%-79% of cases)
Scoliosis	Frequent (present in 30%-79% of cases)
Seizures	Frequent (present in 30%-79% of cases)
Strabismus	Frequent (present in 30%-79% of cases)
Wide mouth	Frequent (present in 30%-79% of cases)
Abnormality of the clavicle	Occasional (present in 5%-29% of cases)
Abnormality of the hip bone	Occasional (present in 5%-29% of cases)
Abnormality of the intervertebral disk	Occasional (present in 5%-29% of cases)
Aplasia/Hypoplasia of the distal phalanx of the 5th toe	Occasional (present in 5%-29% of cases)
Bilateral single transverse palmar creases	Occasional (present in 5%-29% of cases)
Cataract	Occasional (present in 5%-29% of cases)
Congenital diaphragmatic hernia	Occasional (present in 5%-29% of cases)
Coxa valga	Occasional (present in 5%-29% of cases)
Cutis marmorata	Occasional (present in 5%-29% of cases)
Ectopic kidney	Occasional (present in 5%-29% of cases)
Epicanthus	Occasional (present in 5%-29% of cases)
Hydronephrosis	Occasional (present in 5%-29% of cases)
Hypoplasia of the corpus callosum	Occasional (present in 5%-29% of cases)
Hypoplastic fifth toenail	Occasional (present in 5%-29% of cases)
Kyphosis	Occasional (present in 5%-29% of cases)
Lacrimation abnormality	Occasional (present in 5%-29% of cases)
Partial agenesis of the corpus callosum	Occasional (present in 5%-29% of cases)
Ptosis	Occasional (present in 5%-29% of cases)
Renal hypoplasia/aplasia	Occasional (present in 5%-29% of cases)
Short philtrum	Occasional (present in 5%-29% of cases)
Spina bifida occulta	Occasional (present in 5%-29% of cases)
Aggressive behavior	-
Aplasia of the uterus	-
Astigmatism	-
Atrial septal defect	-
Autistic behavior	-
Autosomal recessive inheritance	-
Broad nasal tip	-
Choanal atresia	-
Delayed eruption of teeth	-
Delayed skeletal maturation	-
Dislocated radial head	-
Duodenal ulcer	-
Facial hypertrichosis	-
Gastric ulcer	-
Hemangioma	-
High palate	-
Hypospadias	-
Hypotelorism	-
Inguinal hernia	-
Intestinal malrotation	-
Intussusception	-
Joint laxity	-
Lumbosacral hirsutism	-
Myopia	-
Patent ductus arteriosus	-
Postnatal growth retardation	-
Preauricular skin tag	-
Renal hypoplasia	-
Sacral dimple	-
Severe expressive language delay	-
Short distal phalanx of the 5th finger	-
Short distal phalanx of the 5th toe	-
Short sternum	-
Single transverse palmar crease	-
Sparse scalp hair	-
Tetralogy of Fallot	-
Umbilical hernia	-
Ventricular septal defect	-

Last updated: 9/1/2017

Cause Cause

Coffin-Siris syndrome is caused by a change (mutation) in either the ARID1A, ARID1B, SMARCA4, SMARCB1, or SMARCE1 gene. Exactly how these gene mutations result in the symptoms of Coffin-Siris syndrome is not known, however it is thought that the mutations affect how genetic material is packaged in the cell.

Coffin-Siris syndrome is an autosomal dominant condition; as only one gene mutation is needed to cause the syndrome. It usually occurs for the first time in a family due to a new mutation.

In some cases, no genetic mutation can be identified and the cause of Coffin-Siris syndrome in the family remains unknown.^[1]

Last updated: 1/5/2016

Diagnosis Diagnosis

Diagnosis of Coffin-Siris syndrome is largely based upon the presence or absence of common signs and symptoms in the individual. While formal diagnostic criteria have not been established, most individuals with a clinical diagnosis of Coffin-Siris syndrome have certain features in common.^[2] You can find detailed information on this topic at the following link to GeneReviews.
http://www.ncbi.nlm.nih.gov/books/NBK131811/#coffin-siris.Diagnosis

Genetic testing may also be used to diagnose or confirm cases of Coffin-Siris syndrome.^[2]

Last updated: 1/5/2016

Treatment Treatment

People with Coffin-Siris syndrome may benefit from occupational, physical, and speech therapy. Developmental pediatricians may be helpful in recommending and coordinating therapeutic and educational interventions. Additional specialty care may be needed depending on the symptoms in the individual, such as by gastrointestinal, eye, kidney, heart, and hearing specialists.^[2]

Last updated: 1/5/2016

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. There is a study titled Pediatric Patients With Metabolic or Other Genetic Disorders which may be of interest to you. To find this trial, click on the link above.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

National Foundation for Ectodermal Dysplasias
6 Executive Drive
Suite 2
Fairview Heights, IL 62258-1360
Telephone: 618-566-2020
Fax: +1-618-566-4718
E-mail: info@nfed.org
Website: http://nfed.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference contains information on Coffin-Siris syndrome. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Coffin-Siris syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

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August 31, 2017
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August 10, 2017
Young Investigator Initiative Career Development and Grant Mentoring Program
June 21, 2016

Related Diseases Related Diseases

The following diseases are related to Coffin-Siris syndrome. If you have a question about any of these diseases, you can contact GARD.

Ectodermal dysplasia

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References References

Coffin-Siris Syndrome. Genetics Home Reference. May 2013; http://www.ghr.nlm.nih.gov/condition/coffin-siris-syndrome. Accessed 1/5/2016.
Vergano SS, Santen G, Wieczorek D, Wollnik B, Matsumoto N, Deardorff MA. Coffin-Siris Syndrome. GeneReviews. July 11, 2013; http://www.ncbi.nlm.nih.gov/books/NBK131811/. Accessed 1/5/2016.

Do you know of a review article? Send us your suggestions.