Phenotypic Differences in Multiple Osteochondromas in Monozygotic Twins: A Case Report.

Abstract

As defined by the World Health Organization (WHO), an osteochondroma is a cartilage-capped osseous outgrowth that is broad-based or stemmed and is made up of cortex and a marrow cavity, which are both continuous with the host bone. The Online Mendelian Inheritance in Man (OMIM) categorizes it under number 133700 and terms it hereditary multiple exostoses (HME), a synonym of the WHO term multiple osteochondroma (MO). MO is a monogenic autosomal-dominant disorder, caused by loss-of-function mutations in either exostosin-1 (EXT1) (8q23-q24)1 or exostosin-2 (EXT2) (11p11-p12)2,3. EXT1 and EXT2 mutations are found in 90% of all cases4. Most often, one side is predominantly affected within a person and family, and sidedness rarely shifts5. Possible modulators are sex, age, and gene environment. We report on a pair of monozygotic twins with MO. We found phenotypic differences, and there was a tendency toward mirror-image involvement. We reviewed the literature for explanations, searching for genotype-phenotype relationships and the presence of mirror image or variable disease expression within monozygotic twins. Based on the difference in phenotype in these twins, it seems that mere genetic factors insufficiently explain differences in phenotype. The patients and their parents were informed that data concerning their cases would be submitted for publication, and they provided consent. Ten-year-old monozygotic twin girls presented to our outpatient clinic. Family history was positive for MO in the father, who was known to carry an EXT1 mutation. Molecular analysis by polymorphic DNA markers proved the twins to be monozygotic, and sequence analysis showed a c.572delT (p.Leu191X) mutation in exon 1 of the EXT1 gene. The twins had never undergone surgery before presentation, nor did they have a history of trauma. No specific comorbidity was present in either of the girls. Patient A’s height was measured at …