Clinical Guidance
The clinical manifestations of Coffin-Siris syndrome have expanded over the years as greater phenotypic variability has been recognized. Classically, the syndrome was first identified by the absence or underdevelopment of the fifth digit finger/toe or nail. Additional "classic" features have included sparse scalp hair, hypertrichosis, learning and developmental differences, and various organ system-related anomalies. As genetic technology has evolved, more individuals with subtle physical exam findings are being diagnosed with CSS. To date, at least 550 individuals have been identified with a diagnosis of Coffin-Siris syndrome, including those enrolled in the Coffin-Siris syndrome/ BAF complex registry [; ; ; ; ; ; S Schrier Vergano, unpublished data]. ARID1B has been reported in around 1% of cohorts of individuals with neurodevelopmental disorder . The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Select Features of Coffin-Siris Syndrome
Feature | % of Persons w/Feature | Comment |
|---|
Developmental delay/ intellectual disability | 98% | Typically in the moderate-to-severe range |
Feeding problems | 90% | — |
Hypotonia | 75% | — |
Hypoplasia of the fifth digits/nails1 | 65%-80% | Some individuals with a molecularly confirmed diagnosis of CSS have little or no fifth digit involvement. |
Dysmorphic facial features | 65% | ~30% at birth. Because facial features typically coarsen over time, the characteristic facies may not be apparent until later in childhood. |
Frequent infections | 60% | — |
Other skeletal findings | 40%-60% | Including joint laxity and scoliosis |
Epilepsy | 50% | — |
Hearing impairment | 45% | Both sensorineural and conductive hearing loss has been reported. |
Eye issues | ~40% | Ptosis, strabismus, myopia |
Congenital heart defects | 35% | — |
Genitourinary malformations | 33% | — |
Behavioral issues | 25% | May include hyperactivity /or aggressiveness Typically, individuals with a clinical diagnosis of CSS have either aplasia or hypoplasia of the distal phalanx or absence of the nail, classically involving the fifth finger, but other digits may also be affected. |
Source: GeneReviews — "Coffin-Siris Syndrome"
