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Coffin-Siris syndrome
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Coffin-Siris Syndrome

Coffin-Siris syndrome is a rare genetic condition characterized by developmental delays, distinctive facial features, and abnormalities of the fifth fingers or toes.

Overview

Coffin-Siris syndrome is a condition that affects several body systems. Although there are many variable signs and symptoms, hallmarks of this condition include developmental disability, abnormalities of the fifth (pinky) fingers or toes, and characteristic facial features.

Symptoms and Characteristics

Most affected individuals have mild to severe intellectual disability or delayed development of speech and motor skills such as sitting and walking. Other common features of Coffin-Siris syndrome include:

  • Hypoplasia (underdevelopment) of the tips of the fingers or toes, or hypoplasia or absence of the nails, most commonly affecting the fifth digits.
  • Coarse facial features, typically including a wide nose with a flat nasal bridge, a wide mouth with thick lips, and thick eyebrows and eyelashes.
  • Hirsutism (excess hair on other parts of the face and body), though scalp hair is often sparse.
  • An abnormally small head.
  • Frequent respiratory infections, difficulty feeding, and an inability to gain weight at the expected rate (failure to thrive) in infants and children.
  • Short stature, hypotonia (low muscle tone), and abnormally loose (lax) joints.
  • Abnormalities of the eyes, brain, heart, and kidneys.

Frequency

Coffin-Siris syndrome is a rare condition that, for unknown reasons, is diagnosed in females more frequently than in males. Approximately 200 cases have been reported in the medical literature.

Causes & Genetic Factors

Coffin-Siris syndrome is caused by variants (also known as mutations) in one of several genes. Variants in the ARID1B gene are the most common known cause of the condition. Variants in the following genes can also cause the condition:

  • ARID1A
  • SMARCA4
  • SMARCB1
  • SMARCE1
  • SOX11

Additionally, variants in other genes, including ARID2, DPF2, SMARCC2, and SOX4, have been found to cause a very small number of cases. In some of these cases, it is unclear if the condition should be considered Coffin-Siris syndrome or a similar but separate disorder. In many cases of Coffin-Siris syndrome, the genetic cause is unknown.

These genes are involved in controlling the activity (expression) of other genes. The proteins they produce act as subunits of several different SWI/SNF protein complexes. These complexes regulate gene expression through a process known as chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. By altering how tightly regions of DNA are packaged, chromatin remodeling regulates gene expression during development.

Through chromatin remodeling, SWI/SNF complexes are involved in repairing damaged DNA, replicating DNA, and controlling the growth, division, and differentiation of cells. Researchers suggest that variants in these genes result in abnormal chromatin remodeling, which alters the activity of many genes and disrupts cellular processes, explaining the diverse signs and symptoms of the syndrome.

The SOX11 gene is regulated by SWI/SNF complexes. The protein produced from this gene acts as a transcription factor, which binds to specific regions of DNA to help control gene activity. The SOX11 protein is particularly important for brain development and the differentiation of nerve cells (neurons). Variants in this gene disrupt the protein's ability to control gene activity, altering the development of the brain and neurons, which is thought to lead to intellectual disability and other symptoms of Coffin-Siris syndrome.

Inheritance Pattern

Coffin-Siris syndrome appears to follow an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, the condition is not usually inherited from an affected parent, but occurs from new variants in the gene that likely occur during early embryonic development.

Other Names for This Condition

  • CSS
  • Dwarfism-onychodysplasia
  • Fifth digit syndrome
  • Mental retardation with hypoplastic fifth fingernails and toenails
  • Short stature-onychodysplasia

Frequently Asked Questions

chromosomal microarray may miss single‑gene changes, so a targeted next‑generation sequencing panel or exome sequencing that includes ARID1B, ARID1A, SMARCA4, SMARCB1 and SMARCE1 is recommended. ARID1B variants account for ~60‑70 % of confirmed cases. If a pathogenic variant is found, parental testing can determine if it is de novo or inherited.
Early intervention with a multidisciplinary team—physical therapy to address hypotonia and joint laxity, occupational therapy for fine‑motor skills (especially for the hypoplastic fifth digits), and speech‑language therapy focused on augmentative communication—has been shown to maximize developmental gains. Starting these services before age 2 years yields the best outcomes.
Baseline echocardiogram, renal ultrasound, and ophthalmologic exam should be performed at diagnosis. Follow‑up cardiac imaging every 2–3 years (or sooner if murmurs develop), renal imaging every 3–5 years, and annual eye exams to monitor for strabismus or refractive errors. Additionally, monitor growth parameters and screen for sleep‑disordered breathing if hypotonia is severe.
Watch for poor weight gain despite adequate calories, prolonged feeding times, coughing or choking during feeds, and frequent respiratory infections. A pediatric gastroenterology evaluation may recommend thickened feeds, a specialized feeding schedule, or a nasogastric tube. If oral intake remains insufficient after 4–6 weeks, placement of a gastrostomy tube is often recommended to ensure growth and reduce aspiration risk.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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