A congenital syndrome with growth and mental retardation, feeding difficulties, digital anomalies, and coarse facies.
Fifth Digit Syndrome; Dwarfism-Onychodysplasia Syndrome; Short Stature-Onychodysplasia Syndrome.
First described in 1970 by Grange S. Coffin, an American pediatrician, and Evelyn Siris, an American radiologist. To avoid confusion with the Coffin-Siris-Wegienka Syndrome, it was decided to name the latter syndrome ☞Coffin Lowry Syndrome (after Robert Brian Lowry, a British medical geneticist, who described a fourth family with the findings of Coffin-Siris-Wegienka Syndrome in 1971).
Since its first description, approximately 200 cases have been reported. According to early reports, the male-to-female was quoted as 1:4; however, more recent research describes equal distribution between both genders in genetically proven CSS patients.
Autosomal dominant with almost complete penetrance. However, the majority of patients have a de novo pathogenic variant. Based on the mutations responsible for the disorder, six types of Coffin-Siris Syndrome (CSS) can be distinguished (note that in 40% the genetic defect has not been determined, yet):
Each gene encodes a component of the SWI/SNF complex, which is involved in the modulation of eukaryotic gene expression and DNA repair via nucleosome remodeling.
Until recently, it was based entirely on the clinical findings (see below), but nowadays molecular genetic testing is available and used to confirm the diagnosis.
A constant finding is either hypoplasia or aplasia of the distal phalanx (in about two-thirds of patients) or absence of one or more nail(s) (in approximately 80%), most frequently affecting the fifth finger (hence the synonymous name “Fifth Digit Syndrome”), but other digits may also be affected with absence or hypoplasia of the distal and middle phalanges of fingers and toes. Other frequent features are low birth weight, failure to thrive (in 67%; poor sucking and feeding difficulties), recurrent respiratory tract infections (aspiration), hirsutism/hypertrichosis (in 95%), and low-anterior hairline (in 75%). Central nervous system anomalies may include microcephaly, generalized hypotonia (in 75% of patients), mild-to-moderate mental retardation, variable types of seizures (in 50%), ☞Dandy-Walker Malformation, hypoplasia/agenesis of the corpus callosum, and abnormal and ectopic cerebellar nuclei. Vision problems (ptosis, strabismus, myopia, astigmatism, nystagmus, and tear duct anomalies) and mild-to-severe conductive hearing loss (most likely secondary to recurrent ear infections) are each present in almost half of the patients. Facial features may be subtle at birth, but become more obvious over time and can result in coarse facies with sparse scalp hair (especially in infancy), long eyelashes, and bushy eyebrows. The coarse facies results from dysplastic, posteriorly rotated ears, broad nasal bridge and nasal tip, anteverted nares, choanal atresia, high-arched palate (occasionally with cleft), wide mouth with thick and prominent lips, possible macroglossia, and occasionally short philtrum, and ...