Multiple bilateral hip fractures in a patient with dyskeratosis congenita caused by a novel mutation in the PARN gene

We report a case of a young male patient with clinical signs of dyskeratosis congenita who presented with multiple bilateral low-traumatic hip fractures. Whole exome sequencing (WES) showed a previously unreported mutation in the poly(A)-specific ribonuclease (PARN) gene. Zoledronic acid 5 mg over 3 years was effective at preventing further fractures. A male patient was referred to our clinic at age 24 due to multiple bilateral hip fractures. At the time of admission, the patient's height was 160 cm and weight 40 kg; bone mineral density (BMD) at the lumbar spine was normal (L1-L4 0.0 Z-score). The patient was found to have abnormal skin pigmentation, hyperkeratosis of palms and soles, nail dystrophy, and signs of bone marrow failure (BMF). Bone fragility first presented at 5 years old with a wrist fracture, followed by multiple bilateral low-traumatic hip fractures without falls from 14 to 24 years. WES showed a previously unreported mutation (NM_002582.3: c.1652delA; p.His551fs) in the poly(A)-specific ribonuclease (PARN) gene. Flow fish telomere measurement result was 5.9 (reference range 8.0-12.6), which is consistent with the DC diagnosis. Permanent fixation with internal metal rods and zoledronic acid 5 mg over 3 years was effective at preventing further fractures over 4 years of follow-up. Additionally, BMF did not progress over 4 years of observation. DC associated with PARN gene mutations might predispose to low-traumatic multiple hip fractures in adolescents and young adults. Treatment with zoledronic acid in this case was effective and safe at preventing further fractures.

Automated summary

A young male patient with clinical signs of dyskeratosis congenita presented with multiple bilateral low-traumatic hip fractures. Whole exome sequencing revealed a previously unreported mutation in the PARN gene. Treatment with zoledronic acid was effective at preventing further fractures.