Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia with short stature, sparse hair and defective cell-mediated immunity. It is caused by mutations in the RMRP (ribonuclease mitochondrial RNA processing) gene, encoding the RNA component of the ribonuclease complex RNase MRP. The aim of this study was to further elucidate the risk and spectrum of cancer in CHH. A cohort of 123 Finnish patients with CHH (51 males) was followed for malignancy through the Finnish Cancer Registry. The number of identified cancers was compared with expected numbers of cancer using population-based data to obtain standardized incidence ratios (SIR). Hospital records were reviewed for clinical data related to the malignancies. During the follow-up (2,365 person-years; mean 19.2 years), 14 cases of cancer were diagnosed in the CHH cohort (expected number 2.0; SIR 7.0, CI 3.8-12). Non-Hodgkin lymphoma was the most frequent cancer type (n = 9; SIR 90.2, CI 39.0-180) followed by squamous cell carcinoma (3), leukemia (1) and Hodgkin lymphoma (1). One tumor was not histologically classified. Nine of the 14 cancers were diagnosed in patients less than 45 years of age. In addition, ten patients had basal cell carcinoma of the skin (expected number 0.3; SIR 33.2, CI 16-61). Patients with CHH have significantly increased risk for developing non-Hodgkin lymphoma or basal cell carcinoma at early age; the overall prognosis is poor. The underlying pathogenetic mechanisms remain to be elucidated in future studies. Careful follow-up, extending beyond pediatric age, is warranted for early diagnosis of malignancies.
Copyright 2008 Wiley-Liss, Inc.