Short-limbed dwarfism with bowing, combined immune deficiency, and late onset aplastic anaemia caused by novel mutations in the RMPR gene.

K yphomelic dysplasia has been described as a generalised skeletal dysplasia characterised by a disproportionate growth, bowing of long bones, mild facial dysmorphia, and normal intelligence, with radiologically flattened vertebrae, short ribs, and metaphyseal flaring. Twenty-one cases have been reported in the literature. However the diagnosis in several cases from the literature has been disputed. The case described by Maclean and co-workers was reported recently to have Schwartz-Jampel syndrome, and the family reported by Toledo et al in fact had osteogenesis imperfecta. This led Spranger et al to suggest that kyphomelic dysplasia does not exist. However, there is still a group of cases described as kyphomelic dysplasia, which do not fit the profile of these or other disorders that manifest as dwarfism and kyphomelia. The cases can be distinguished from campomelic dysplasia by the extraskeletal manifestations, mental retardation, ambiguous genitalia, severe tibial bowing, and hypoplastic scapulae in the latter, and from femoral hypoplasia-unusual facies syndrome by the hypoplasia of the femur. Several single case reports that show a related but still different phenotype have been described. Short-limbed dwarfism with normal intelligence does also occur in cartilage-hair hypoplasia (CHH; MIM 250250). Apart from dwarfism, major symptoms include fine, sparse hair, marked hypermobility of the smaller joints with short phalanges, and a variable immunodeficiency. Radiologically, the metaphyses are scalloped and sclerotic, especially around the knees, ankles, and anterior angulation of the entire sternum. The femur can be bowed, but usually only mildly so. There is no platyspondyly. CHH presenting in infancy can be difficult to diagnose. 24 Mutations in the RMRP gene that codes for an RNA subunit of the mitochondrial RNA processing (MRP) RNAse complexes are the cause of CHH, with a common "Finnish" mutation +70ARG (A70G) in many of the known CHH patients. 26 Here we report on a case with short-limb dwarfism diagnosed as having kyphomelic dysplasia in infancy, who developed severe aplastic anaemia, concurring with a combined immune deficiency of late onset. She received a successful allogeneic bone marrow transplant. The phenotype gradually changed and became more typical of CHH. Mutation analysis subsequently showed two novel mutations in the RMRP gene.