Coffin-Siris syndrome and differential diagnosis [26 genes]

Coffin-Siris syndrome is classically characterized by aplasia or hypoplasia of the distal phalanx and/or nail of the fifth and additional fingers, developmental delay of variable degree, characteristic facial features, hypotonia, hirsutism/hypertrichosis and sparse hair on the scalp. Other congenital anomalies could be cardiac, gastrointestinal, genitourinary, and/or central nervous system malformations. Other common findings are feeding difficulties, growth delay, ophthalmological abnormalities, and hearing deficiencies.

Coffin-Siris syndrome: <1 / 1,000,000 (ORPHA:1465).

The benefits derived from a genetic diagnosis in this context can range from family genetic counseling, typical of genetic studies in general, to the early detection of associated comorbidities to achieve better symptomatic management.

Service indicated in the presence of findings suggestive of the disease and, therefore, when there is at least moderate clinical suspicion of having this syndrome.

The diagnostic yield in this disease is relatively low, with up to 40% of patients with a clinical diagnosis in whom no molecular alteration is found in the genes known to date. 60% of patients pathogenic variants are usually alterations in the nucleotide sequence and, more rarely, CNVs that can be identified, a priori, using an exome-based approach.