title: Cartilage-hair hypoplasia with normal height in childhood-4 patients with a unique genotype.
abstract: 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.
authors.affiliation: Children's Hospital, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Klemetti
authors.affiliation: Children's Hospital, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Valta
authors.affiliation: Children's Hospital, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.|Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Kostjukovits
authors.affiliation: Children's Hospital, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Taskinen
authors.affiliation: Helsinki Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Toiviainen-Salo
authors.affiliation: Children's Hospital, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.|Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland.|Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: O
authors.initials: O
authors.lastname: Mäkitie
mesh_terms: D000328:Adult; D001827:Body Height / Q000235:genetics; D002648:Child; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006197:Hair / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000503:physiopathology; D006627:Hirschsprung Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D010009:Osteochondrodysplasias / Q000151:congenital* / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D000081207:Primary Immunodeficiency Diseases; D062085:RNA, Long Noncoding / Q000235:genetics*; D011859:Radiography; D055815:Young Adult
chemical_list: C544035:RMRP non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: 
  RMRP
  ; immunodeficiency; non-Hodgkin lymphoma; short stature; skeletal dysplasia