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Cartilage‐hair hypoplasia with normal height in childhood—4 patients with a unique genotype
Author(s) -
Klemetti P.,
Valta H.,
Kostjukovits S.,
Taskinen M.,
ToiviainenSalo S.,
Mäkitie O.
Publication year - 2017
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12969
Subject(s) - short stature , hypoplasia , osteochondrodysplasia , genotype , medicine , dysplasia , bronchiectasis , compound heterozygosity , failure to thrive , bone age , pediatrics , endocrinology , gastroenterology , mutation , genetics , biology , pathology , lung , gene
The manifestations of cartilage‐hair hypoplasia ( CHH ), a metaphyseal chondrodysplasia caused by RMRP mutations, include short stature, hypoplastic hair, immunodeficiency and increased risk of malignancies. Clinical features show significant variability. We report a patient with normal height until age 12.5 years (−1.6 SDS at 11 years) who was diagnosed with CHH at 14 years. RMRP sequencing revealed compound heterozygosity for g. 70A >G mutation and a 10‐nucleotide duplication at position −13 ( TACTCTGTGA ). Through the Finnish Skeletal Dysplasia Register, we identified 3 additional patients with identical genotype. Two of them also showed unusually mild growth failure (height SDS −1.6 at 14 years and −3.0 at 12 years, respectively). Three of the 4 patients suffered from recurrent infections; 1 developed progressive bronchiectasis and another died from aggressive lymphoma. Our findings expand the phenotypic variability in CHH to include normal childhood height. The milder growth retardation related to this particular genotype was not associated with less severe extra‐skeletal manifestations, emphasizing the need for careful follow‐up also in CHH patients with mild‐skeletal manifestations.