[en] Deletions in chromosome 14q22-23 have been associated with variable manifestations including malformations of the eye, limbs, palate and brain, and developmental and growth delay. Haploinsufficiency for BMP4, OTX2 and possibly SIX6 are thought to contribute to the phenotype. We present a three generation family with 4 individuals carrying a 2.79Mb microdeletion 14q22.1-22.2 encopassing BMP4 but not OTX2 nor SIX6. The highly variable manifestations in this family range from multiple congenital malformations with Robin sequence, microphthalmia, postaxial polydactyly and developmental delay in the index patient and cleft uvula, growth delay and mild developmental delay in her sister. The adults have a normal intelligence, postaxial polydactyly and short stature or early cataract. Genotype-phenotype correlations suggest that the severity of eye manifestations in 14q22 deletions are influenced by the size of the deletion, but the marked intrafamilial variability observed in this family, as well as in familial BMP4 or OTX2 intragenic mutations points to additional modifiers outside this region.
