A consultation in
Medical Genetics

A child had recurrent swelling, progressive stiffness and loss of mobility. Cancer was initially suspected and treated for months, but that explanation did not account for the full course of the condition.

Could a genetic condition explain bone formation outside the skeleton and the loss of mobility?

A combined review of the history, examination and X-rays showed heterotopic ossification and skeletal abnormalities. This suggested fibrodysplasia ossificans progressiva. Exome analysis identified a causative ACVR1 variant.

The diagnosis redirected care away from a presumed tumour, helped avoid procedures that could worsen the condition, and supported preventive and multidisciplinary follow-up. Access to a clinical trial was later considered; this does not imply a proven treatment benefit.

From adolescence, a young person developed myoclonus, seizures, falls and progressive motor difficulties. Intellectual ability remained intact, but a unifying explanation was still missing.

How could a NEU1 finding be interpreted when one variant was still classified as having uncertain significance?

Examination identified cherry-red spots in the retina. Family studies and a functional fibroblast test, performed with a collaborating laboratory, showed reduced sialidase activity. Together with the clinical findings, this supported a diagnosis of type I sialidosis.

A diagnosis made it possible to organise neurological follow-up, rehabilitation, fall prevention and seizure management. It also helped clarify that motor limitations should not be mistaken for intellectual decline.

A child with metastatic papillary thyroid carcinoma still had detectable disease after surgery and radioiodine. The treating team needed to assess whether the tumour profile offered another option.

Was there a molecular alteration that could inform an individual treatment decision?

Tumour sequencing, liquid biopsy and multidisciplinary discussion identified a CCDC6-RET fusion. The finding was interpreted alongside the clinical course, previous treatment and available alternatives.

The finding allowed the team to consider selective RET-targeted therapy, such as selpercatinib. This case illustrates how a molecular result can inform options; it does not report a treatment outcome or recommend the same approach for other patients.