Compelling Case Of Copper Conundrum: Occipital Horn Syndrome

Background: Occipital horn syndrome (OHS) is a very rare, X-linked genetic disorder. There are 20 cases reported. It is a disorder of copper metabolism caused by missense mutations in the ATP7A gene, leading to toxic cellular accumulation of copper. This is the less severe phenotype of the condition known as the childhood variant of Menkes disease. We present a case report of a male with this syndrome who evaded clinical diagnosis for many years, with interesting radiological findings of rib notching which has not been associated with this condition.

Methods: A 25 year old male presented with a diaphyseal skeletal dysplasia with abnormal carpal bones, radial shortening, humeral abnormalities, abnormal femoral head development and exostoses. Of note were inferior and superior rib notching. As a child, he was noted to have hypotonia, skin laxity, hyper-extensible joints and delayed developmental milestones. During his teenage years, he suffered from short stature and delayed puberty. He had experienced considerable myalgia and polyarthralgia with associated weakness compounded by pain and fatigue. He required multiple surgical interventions for para-umbilical, femoral and inguinal hernias since infancy. He was treated for multiple bladder infections secondary to diverticula; leading to numerous surgeries, including a left sided nephrectomy for non-functioning kidney. He was diagnosed with mitral valve prolapse as a child. Recently, he has suffered from short lived irregular palpitations with dyspnoea, triggered by posture changes. He had prolonged QTc interval on electrocardiogram but cardiac MRI was unremarkable. On examination, he demonstrated a long neck and forehead with narrow face, elevated arched palate and micrognathia. There was evidence of lax skin, reduced subcutaneous fat and markedly hypermobile joints. There was marked exostosis at the elbows with fused radial heads. He had narrow shoulders with expanded clavicular-sternal joints, as well as pectus excavatum.

Results: On specialist review of the patient’s skeletal imaging, large exostoses (calcifications) were found in his trapezius and sternocleidomastoid muscles. These are the characteristic occipital horns, which married together with the spectrum of the connective tissue phenotype led to confirmatory blood and genetic testing showing low plasma copper and caeruloplasmin as well as the pathogenic mutation. Subcutaneous copper histidine replacement injections have been tried in Menkes disease and it is thought to slow disease progression. The use of copper in OHS is less certain.

Conclusion: Occipital horn syndrome is worth considering as a diagnosis in cases with specific connective tissue phenotypes and odd radiological features. Inferior and superior rib notching has a short differential list and OHS should be added to this. This case illustrates the need for multiprofessional specialist services including the clinical genetics department. Diagnosis is important to establish in terms of monitoring organ complications and to plan antenatal screening and treatments that may improve long-term outcome.