Rare clinical findings in three sporadic cases of Beckwith-Wiedemann syndrome due to novel mutations in the CDKN1C gene

Beckwith-Wiedemann syndrome (BWS) is a rare congenital overgrowth disorder characterised by macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralised overgrowth and predisposition to embryonal tumours. BWS results mainly from epigenetic changes at chromosome 11p15.5; however, heterozygous pathogenic variants on the maternalCDKN1Callele are observed in 5-8% of sporadic BWS cases. In this study, we report three sporadic BWS patients with novel pathogenic variants in theCDKN1Cgene, including one missense (c.181T>C) and two frameshift (c.415_416dup, c.804delC). Detailed clinical evaluation of the patients showed variable manifestation of the disease and underlined the diagnostic challenge for BWS patients at various age of life. The child with the c.415_416dup variant presented with two rare features observed so far in only a few BWS patients withCDKN1Cpathogenic variants: supernumerary flexion creases and agenesis of corpus callosum. Confirmation of these findings in another BWS patient adds to the broad clinical spectrum of the disease and suggests that presence of these features may be associated withCDKN1Cpathogenic variants.