The Coffin-Siris syndrome: a proposed diagnostic approach and assessment of 15 overlapping cases.
Coffin-Siris syndrome (CSS) is a rare, clinically heterogeneous disorder often considered in the setting of cognitive/developmental delay and 5th finger/nail hypoplasia. Due to the clinical variability of facial and other features, this diagnosis is often difficult to confirm clinically and the existence of this disorder as a specific diagnosis has been at times an issue of debate. In an effort to further delineate the spectrum and key phenotypic features, we reviewed 80 previously reported cases to define features in patients that most closely correlated with a convincing diagnosis. There appear to be two subtypes of CSS, one which displays the "classic" coarse facial features previously described; another displays "variant" facial features which are less striking. Using these features, we defined an algorithm to rank the confidence of diagnosis and applied it to 15 additional patients who had been previously characterized by chromosome microarray. This approach will also facilitate uniform categorization for whole-exome analysis.
Division of Human Genetics, The Children's Hospital of Philadelphia, and Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Samantha A
SA
Schrier
Joann N
JN
Bodurtha
Barbara
B
Burton
Albert E
AE
Chudley
Mary Anne D
MA
Chiong
Maria Gabriella
MG
D'avanzo
Sally Ann
SA
Lynch
Antonio
A
Musio
Dmitriy M
DM
Nyazov
Pedro A
PA
Sanchez-Lara
Stavit A
SA
Shalev
Matthew A
MA
Deardorff
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000465:Algorithms; D005145:Face / Q000002:abnormalities; D005260:Female; D006228:Hand Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008844:Micrognathism / Q000175:diagnosis* / Q000235:genetics; D009333:Neck / Q000002:abnormalities; D020641:Polymorphism, Single Nucleotide