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

This disease is grouped under:

Ectodermal dysplasia

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, DPF2 or SMARCE1 genes.^[1] 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.^[2] Occupational, physical, and/or speech therapy can help affected individuals reach their full potential.^[3]

Last updated: 1/5/2016

Symptoms Symptoms

The signs and symptoms of Coffin-Siris syndrome vary. More commonly described symptoms include:^[2]

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:^[2]

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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of the dentition	Abnormal dentition Abnormal teeth Dental abnormality [ more ]	0000164
Aplasia/Hypoplasia of the distal phalanx of the 5th finger	Absent/small outermost bone of little finger Absent/small outermost bone of pinkie finger Absent/small outermost bone of pinky finger Absent/underdeveloped outermost bone of pinky finger [ more ]	0009239
Coarse facial features	Coarse facial appearance	0000280
Feeding difficulties in infancy		0008872
Generalized hirsutism	Excessive hairiness over body	0002230
Global developmental delay		0001263
Hypoplastic fifth fingernail	Underdeveloped fifth fingernail Underdeveloped fingernail of little finger Underdeveloped fingernail of pinkie finger Underdeveloped fingernail of pinky finger [ more ]	0008398
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Long eyelashes	Increased length of eyelashes Unusually long eyelashes [ more ]	0000527
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Muscular hypotonia	Low or weak muscle tone	0001252
Short distal phalanx of finger	Short outermost finger bone	0009882
Short stature	Decreased body height Small stature [ more ]	0004322
Slow-growing hair	Slow growing hair Slow rate of hair growth Slow speed of hair growth [ more ]	0002217
Thick eyebrow	Bushy eyebrows Dense eyebrow Heavy eyebrows Prominent eyebrows Thick eyebrows [ more ]	0000574
Thick lower lip vermilion	Increased volume of lower lip Plump lower lip Prominent lower lip [ more ]	0000179
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431
30%-79% of people have these symptoms
Abnormality of cardiovascular system morphology		0030680
Aplasia/Hypoplasia of the cerebellum	Absent/small cerebellum Absent/underdeveloped cerebellum [ more ]	0007360
Aplasia/Hypoplasia of the patella	Absent/small kneecap Absent/underdeveloped kneecap [ more ]	0006498
Cryptorchidism	Undescended testes Undescended testis [ more ]	0000028
Dandy-Walker malformation		0001305
Depressed nasal bridge	Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ]	0005280
Depressed nasal ridge	Flat nose Recessed nasal ridge [ more ]	0000457
Elbow dislocation	Dislocations of the elbows Elbow dislocations [ more ]	0003042
Hearing impairment	Deafness Hearing defect [ more ]	0000365
Intrauterine growth retardation	Prenatal growth deficiency Prenatal growth retardation [ more ]	0001511
Joint hyperflexibility	Joints move beyond expected range of motion	0005692
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Recurrent respiratory infections	Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ]	0002205
Scoliosis		0002650
Seizure		0001250
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Wide mouth	Broad mouth Large mouth [ more ]	0000154
5%-29% of people have these symptoms
Abnormality of the clavicle	Abnormal collarbone	0000889
Abnormality of the hip bone	Abnormality of the hips	0003272
Abnormality of the intervertebral disk		0005108
Aplasia/Hypoplasia of the distal phalanx of the 5th toe	Absent/small outermost little toe bone Absent/small outermost pinkie toe bone Absent/small outermost pinky toe bone Absent/underdeveloped outermost pinky toe bone [ more ]	0100371
Bilateral single transverse palmar creases		0007598
Cataract	Clouding of the lens of the eye Cloudy lens [ more ]	0000518
Cleft palate	Cleft roof of mouth	0000175
Congenital diaphragmatic hernia		0000776
Coxa valga		0002673
Cutis marmorata		0000965
Ectopic kidney	Abnormal kidney location Displaced kidney [ more ]	0000086
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Hydronephrosis		0000126
Hypoplasia of the corpus callosum	Underdevelopment of part of brain called corpus callosum	0002079
Hypoplastic fifth toenail	Small fifth toenail Underdeveloped fifth toenail [ more ]	0011937
Kyphosis	Hunched back Round back [ more ]	0002808
Lacrimation abnormality	Abnormality of tear production	0000632
Partial agenesis of the corpus callosum		0001338
Ptosis	Drooping upper eyelid	0000508
Renal hypoplasia/aplasia	Absent/small kidney Absent/underdeveloped kidney [ more ]	0008678
Short philtrum		0000322
Spina bifida occulta		0003298
1%-4% of people have these symptoms
Obsessive-compulsive behavior	Obsessive compulsive behavior	0000722
Percent of people who have these symptoms is not available through HPO
Abnormality of the pinna	Abnormally shaped ears Auricular malformation Deformed ears Malformed ears [ more ]	0000377
Aggressive behavior	Aggression Aggressive behaviour Aggressiveness [ more ]	0000718
Anonychia	Absent nails Aplastic nails [ more ]	0001798
Aplasia of the uterus	Absent uterus uterus absent [ more ]	0000151
Astigmatism	Abnormal curving of the cornea or lens of the eye	0000483
Atrial septal defect	An opening in the wall separating the top two chambers of the heart Hole in heart wall separating two upper heart chambers [ more ]	0001631
Autistic behavior		0000729
Autosomal dominant inheritance		0000006
Autosomal recessive inheritance		0000007
Broad nasal tip	Broad tip of nose Broad, upturned nose Increased breadth of nasal tip Increased breadth of tip of nose Increased width of nasal tip Increased width of tip of nose Nasal tip, broad Nasal tip, wide Wide tip of nose [ more ]	0000455
Choanal atresia	Blockage of the rear opening of the nasal cavity Obstruction of the rear opening of the nasal cavity [ more ]	0000453
Delayed eruption of teeth	Delayed eruption Delayed teeth eruption Delayed tooth eruption Eruption, delayed Late eruption of teeth Late tooth eruption [ more ]	0000684
Delayed skeletal maturation	Delayed bone maturation Delayed skeletal development [ more ]	0002750
Dislocated radial head		0003083
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Duodenal ulcer		0002588
Facial hypertrichosis	Increased facial hair growth	0002219
Gastric ulcer	Stomach ulcer	0002592
Hemangioma	Strawberry mark	0001028
High palate	Elevated palate Increased palatal height [ more ]	0000218
High pitched voice		0001620
Hoarse voice	Hoarseness Husky voice [ more ]	0001609
Hypospadias		0000047
Hypotelorism	Abnormally close eyes Closely spaced eyes [ more ]	0000601
Inguinal hernia		0000023
Intestinal malrotation		0002566
Intussusception		0002576
Joint laxity	Joint instability Lax joints Loose-jointedness Loosejointedness [ more ]	0001388
Low-set ears	Low set ears Lowset ears [ more ]	0000369
Lumbosacral hirsutism		0009747
Myopia	Close sighted Near sighted Near sightedness Nearsightedness [ more ]	0000545
Patent ductus arteriosus		0001643
Posteriorly rotated ears	Ears rotated toward back of head	0000358
Postnatal growth retardation	Growth delay as children	0008897
Preauricular skin tag		0000384
Prominent fingertip pads	Prominent finger pads	0001212
Prominent interphalangeal joints	Prominent hinge joints	0006237
Renal hypoplasia	Small kidneys Underdeveloped kidneys [ more ]	0000089
Sacral dimple	Spinal dimple	0000960
Severe expressive language delay		0006863
Short chin	Decreased height of chin Short lower third of face [ more ]	0000331
Short distal phalanx of the 5th finger	Short outermost little finger bone Short outermost pinkie finger bone Short outermost pinky finger bone [ more ]	0004227
Short distal phalanx of the 5th toe	Short outermost bone of the little toe Short outermost bone of the pinkie toe Short outermost bone of the pinky toe [ more ]	0100391
Short sternum		0000879
Single transverse palmar crease		0000954
Sparse scalp hair	Reduced/lack of hair on scalp Scalp hair, thinning Sparse, thin scalp hair sparse-absent scalp hair [ more ]	0002209
Tetralogy of Fallot		0001636
Thin upper lip vermilion	Thin upper lip	0000219
Umbilical hernia		0001537
Ventricular septal defect	Hole in heart wall separating two lower heart chambers	0001629
Visual impairment	Impaired vision Loss of eyesight Poor vision [ more ]	0000505

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 7/1/2020

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Coffin-Siris syndrome is caused by a change (mutation) in either the ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCE1 or DPF2 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.^[2]

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.^[3] Detailed information on the diagnosis of this condition is available through GeneReviews.

Genetic testing may also be used to diagnose or confirm cases of Coffin-Siris syndrome.^[3]

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.^[3]

Last updated: 1/5/2016

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include Nicolaides-Baraitser syndrome, brachymorphism-onychodysplasia-dysphalangism, DOOR syndrome, hyperphosphatasia-intellectual deficiency syndrome, Borjeson-Forssman-Lehmann syndrome, Wiedemann-Steiner syndrome, Rubinstein-Taybi syndrome and Cornelia de Lange syndrome. Fetal hydantoin syndrome may mimick Coffin-Siris syndrome. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Differential diagnoses include Nicolaides-Baraitser syndrome, brachymorphism-onychodysplasia-dysphalangism, DOOR syndrome, hyperphosphatasia-intellectual deficiency syndrome, Borjeson-Forssman-Lehmann syndrome, Wiedemann-Steiner syndrome, Rubinstein-Taybi syndrome and Cornelia de Lange syndrome. Fetal hydantoin syndrome may mimick Coffin-Siris syndrome.

Visit the Orphanet disease page for more information.

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.

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Coffin-Siris syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for Coffin-Siris syndrome:
Simons SearchLight

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

Coffin-Siris Syndrome Foundation
11611 106th Ave NE
Kirkland, WA 98034
E-mail: coffinsiris@gmail.com
Website: https://www.coffinsiris.org/
National Foundation for Ectodermal Dysplasias
6 Executive Drive
Suite 2
Fairview Heights, IL 62258-1360
Telephone: +1-618-566-2020
Fax: +1-618-566-4718
E-mail: info@nfed.org
Website: https://www.nfed.org/

Do you know of an organization? We want to hear from you.

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

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.
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

NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Knapp K, Poke G, Jenkins D, Truter N, Bicknell L. Expanding the phenotype spectrum associated with DPF2: A new case report. American Journal of Medical Genetics. June 17, 2019; 1-5. https://www.ncbi.nlm.nih.gov/pubmed/31207137.
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.

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