Background:
Osteopetrosis is a rare genetic disorder that causes abnormally dense bones, increasing fracture risk. Autosomal dominant forms affect approximately 1:20,000 people, whereas autosomal recessive cases affect 1:250,000 people. Rarely, X-linked inheritance can also occur. It is also associated with optic nerve compression and hearing loss due to sclerosis of the skull base, as well as odontomas and mandibular osteomyelitis.
Clinical case:
A 60 year old Caucasian gentleman with a background of renal calculi and Osgood-Schlatter disease presented with generalised bilateral knee pain that progressively worsened over 6 months prior to outpatient review. Examination revealed noticeable difficulty in sitting and standing manoeuvres, as well as limited range of motion on flexion and extension of the knees. X-ray imaging of the knees revealed severe tricompartmental degenerative changes and patchy areas of mixed sclerosis and lucency. BMD-DEXA values were markedly elevated globally; L2-L4 T-score +14.4 SD, L total hip T-score +16.9 SD, R total hip T-score +17.3 SD, TBS 1.44. NM bone scan displayed a classical ‘superscan’ pattern. Spinal imaging demonstrated a ‘rugger-jersey’ vertebrae appearance. Other imaging showed dense long bone cortices and increased skull base thickness. These features are clinically suggestive of CLCN7 autosomal dominant osteopetrosis (1), which would have significant clinical implications for his three children, who are currently well. Interestingly, on genetic testing no focal mutation was identified. This represents a case where a novel mutation may be contributory to the diagnosis, given over 95% of pathogenic variants causing osteopetrosis are routinely confirmed on testing of the CLCN7 gene otherwise (2). The patient is currently being managed symptomatically for pain and is limiting mobility on inclines given discomfort associated with this.