Bilaterally cleft lip and bilateral thumb polydactyly with triphalangeal component in a patient with two De novo deletions of HSA 4q32 and 4q34 involving PDGFC , GRIA 2 , and FBXO 8 genes

We report on a newborn boy with a bilateral cleft of the primary palate, duplicated triphalangeal thumbs, and a patent foramen ovale. During childhood he had moderate developmental delay. Brain MRI at 4 years was normal. The concurrence of non‐syndromic clefts of the lip/palate (CL/P) and duplicated thumbs with triphalangeal component has, to our knowledge, not been reported so far. In our case, array‐CGH analysis documented two de novo deletions (∼1.2 Mb and ∼400 Kb) of the long arm of chromosome 4, containing four genes: platelet‐derived growth factor C ( PDGFC ), glycine receptor beta subunit ( GLRB ), glutamate receptor ionotropic AMPA2 ( GRIA2 ), and F‐box protein 8 gene ( FBXO8 ). PDGFC codes for a mesenchymal cell growth factor already known to be associated with clefts of the lip. Pdgfc −/− mice have skeletal anomalies, and facial schisis resembling human cleft/lip palate. GRIA2 codes for a ligand‐activated cation channel that mediates the fast component of postsynaptic excitatory currents in neurons, and may be linked to cognitive dysfunction. FBXO8 , a gene of unknown function, is a member of the F‐box gene family, among which FBXW4 , within the minimal duplicated region associated with human split‐hand/foot malformation type 3 (SHFM type 3). The presence of overlapping deletions in patients who do not share the same phenotype of our case suggests incomplete penetrance, and a possible effect of modifier genetic factors. © 2013 Wiley Periodicals, Inc.