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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 maternal CDKN1C allele are observed in 5-8% of sporadic BWS cases. In this study, we report three sporadic BWS patients with novel pathogenic variants in the CDKN1C gene, 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 with CDKN1C pathogenic 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 with CDKN1C pathogenic variants.

We report four children with unusual facial features including severe blepharophimosis, ptosis, and a distinctive nose with a broad flat tip and a depressed bridge. All four patients were markedly hypotonic and had severe feeding difficulties and developmental delay. Two had congenital heart defects and all three who survived had hypoplastic teeth. Both of the male patients had cryptorchidism. These four children have a distinctive syndrome which is similar to that reported by Biesecker (J Med Genet (1991) 28: 131-134).