Endocrine Abstracts

JOINT3309

Introduction: Cartilage-Hair Hypoplasia (CHH) is presenting as a group of disorders resulting from mutations in the RMRP gene, which produces a non-coding RNA to which proteins bind to form an enzyme called mitochondrial RNA processing endoribonuclease (RNaseMRP). The RNaseMRP enzyme is involved in important cellular processes (DNA replication in mitochondria/ribosome assembly/cell cycle control). Biallelic loss-of-function mutations in RMRP have been reported in individuals with CHH, which present clinically as growth failure/skeletal abnormalities (metaphyseal dysplasia/brachydactyly/delta-shaped epiphyses) and extraskeletal features (hair hypoplasia/immunodeficiencies/anemia/malignancies). The aim is to present a girl with short stature with continuous failure to growth, thin scalp hair and concomitant pathological radiological findings.

Patients/Methods: A 13-year-old adolescent girl (height 128cm/Tanner stage III/no menarche) has been followed since the age of 23/12 years. She is the 4th child of parents with tall stature (father187cm/mother170cm/without phenotypic deformities), born by cesarean section (weight 3010gr/length 50cm). Individual’s history reports a decrease in body length and growth rate since infancy, whereas family history reveals father with a single kidney/mother with cardiac arrhythmia. At the first visit short stature/lordosis of the spine/short phalanges of the fingers of upper and lower extremities/mild varus knee patterns/hyperextensibility of the joints and fine hair on the head were found. Radiologically, widening and hardening of the articular surfaces with a beak-like appearance on the medial surface were found. A comprehensive investigation was performed (nutrition/karyotype/growth hormone secretion tests/thyroid function/celiac disease/bone metabolism). Genetic analysis of the RMRP gene was performed.

Results: Laboratory investigation revealed normal findings. The short stature gradually worsened with a striking increase in the asymmetry of the upper/lower body ratio. The patient presented with multiple lateral elbow dislocations. New bone metabolism tests showed pathological findings (low procollagen I levels/high DPD/cre levels), indicative of reduced bone formation-increased bone resorption. The combination of clinical and laboratory findings led to genetic testing for skeletal malformations and RMRP gene, which confirmed the patient’s double heterozygosity of RMRPn.97_98dup mutation (pathogenic) and RMRPn.25_-12dup mutation (likely pathogenic), inherited from the father and mother, respectively. The patient is closely monitored for growth/puberty but also for early diagnosis of any concomitant events of the disease (immunodeficiencies/malignancies/anemia).

Conclusions: This rare case is the first description of CHH in Greece. In the diagnosis of the disease, clinical and radiological suspicion is very important. RMRP gene should also be required in genetic testing since its mutations lead to early diagnosis of comorbidities that are crucial for the patients’ lives.