National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Coffin-Siris syndrome


Other Names:
Fifth digit syndrome; Intellectual disability with absent fifth fingernail and terminal phalanx
Categories:
This disease is grouped under:
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

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.

Showing of 108 |
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
Showing of 108 |
Last updated: 7/1/2020
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 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

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

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

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.

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
     

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

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.

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.

  1. 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.
  2. Coffin-Siris Syndrome. Genetics Home Reference. May 2013; http://www.ghr.nlm.nih.gov/condition/coffin-siris-syndrome. Accessed 1/5/2016.
  3. 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.