Hereditary multiple exostoses, macrocephaly, congenital heart disease, developmental delay, and mental retardation in a female patient: A possible new syndrome? Or new association?

AbstractHereditary multiple exostoses (HME) or multiple osteochondromas are an autosomal dominant condition and are genetically heterogeneous. It is characterized by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. HME type-I is caused by mutation in the gene encoding exostosin-1 EXT1, which maps to chromosome 8q24. Type-II is caused by mutation in the gene encoding exostosin-2 EXT2 on chromosome 11p12-p11; and type III has been mapped to a locus on chromosome 19, EXT3. We report a de novo case of HME at the Kuwait medical genetic centre (KMGC) came for consultation regarding her poor school performance. She has painless bony swellings over her extremities, macrocephaly, congenital heart disease, obesity, history of developmental delay, and moderate mental retardation. Fluorescent In Situ Hybridization (FISH) analysis done using probes specific for regions 8p22/CEP8/& 8q24.12-8q24.13 showed delineation of two copies of normal sized chromosome 8; also Cycline D1 for 11q13 locus and CEP11, telomeric regions 11q & 11p, all showed normal signals. Telomeric 19p was used to rule out any deletion of 19p and was normal too