Definition
- Also called metaphyseal chondrodysplasia, McKusick type
- Short limb skeletal dysplasia
- Fine sparse hair and immunodeficiency
Aetiology
- Autosomal recessive, from RMRP mutations on chromosome 9p
- RMRP is a noncoding RNA gene in ribosome assembly, cell cycle and mitochondrial DNA replication
- Founder mutations in the Old Order Amish and in Finland
- Same gene causes metaphyseal dysplasia without hypotrichosis and anauxetic dysplasia
Clinical Features
- Disproportionate short limb short stature from infancy
- Fine, sparse, light hair of scalp, eyebrows and eyelashes
- Short broad hands with lax fingers and short nails
- Limited elbow extension
- Genu varum, with ankle deformity from distal fibular overgrowth
- Chest deformity and exaggerated lumbar lordosis
- Normal intelligence
- T cell immunodeficiency with severe or fatal varicella
- Macrocytic anaemia in infancy, often resolving
- Hirschsprung disease, malabsorption and bronchiectasis
- Increased lymphoma and skin cancer risk
Investigations
- Metaphyseal flaring, irregularity, scalloping and sclerosis, most marked at the knees
- Normal or near normal epiphyses
- Short tubular hand bones with cone-shaped epiphyses
- Distal fibula long relative to the tibia
- Spine normal or mildly affected
Differential Diagnosis
- Schmid type, autosomal dominant (COL10A1), milder, coxa vara, normal hair and immunity
- Jansen type, autosomal dominant (PTH1R), severe, with hypercalcaemia
- Shwachman-Diamond syndrome, with pancreatic insufficiency and neutropenia
- Rickets, excluded by normal calcium, phosphate and alkaline phosphatase
- Achondroplasia, with rhizomelic shortening, macrocephaly and normal hair
Management
- Immunological assessment in all patients
- Avoid live vaccines including varicella in significant immunodeficiency
- Treat varicella exposure promptly
- Immunoglobulin for antibody deficiency, stem cell transplantation for severe combined immunodeficiency
- Transplantation corrects the immune defect with no effect on the skeletal dysplasia
- Guided growth or osteotomy for progressive genu varum and ankle deformity
- Growth hormone has limited effect on final height
- Monitor long term for malignancy
Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 10 October 2026.