Disease Profile

Coffin-Siris syndrome

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of Onset

Neonatal

ICD-10

Q87.1

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other Names (AKA)

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

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

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]

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

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.

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
Abnormal clavicle morphology
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

Cause

Coffin-Siris syndrome is caused by a change (mutation) in either the ARID1A, ARID1B, SMARCA4, SMARCB1SMARCE1 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]

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]

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]

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

    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.

        References

        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; https://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; https://www.ncbi.nlm.nih.gov/books/NBK131811/. Accessed 1/5/2016.