Spring BHD Case Report Round-Up

Our spring case report round-up features 3 papers identifying unusual cases of BHD. The first 2 report cases of BHD alongside other genetic mutations. The last paper documents the first account of 2 different mutations in folliculin (FLCN) in the same individual.

Case Report 1

A 55-year-old male had reported shortness of breath, chest tightness and a cough. In the past 2 years, he had been to hospital 4 times for a collapsed lung (pneumothorax). A CT scan of his lungs showed numerous lung cysts and his right lung was collapsed. He had no kidney tumours or skin lesions, and all other tests were normal. However, his fingers on both hands had visible differences and were not fully extended. The patient’s son also had similar fingers and a history of collapsed lungs. Genetic testing revealed that both the patient and their son had mutations in FLCN and another gene called FBN2. The diagnosis of these individuals was BHD and congenital contractural arachnodactyly (CCA). CCA is a rare inherited connective tissue disorder and was the cause of the hand symptoms. It can sometimes be confused with another disorder called Marfan syndrome. Marfan syndrome can also cause collapsed lungs. This report highlights the importance of genetic testing and getting the right diagnosis. The correct management strategies for BHD, including regular kidney scans, can now be put in place to minimise the risk of kidney cancer.

Case Report 2

A 56-year-old woman was referred to the cancer genetics counselling service due to her history of multiple cancers. She had 2 melanomas (skin cancers), thyroid, parathyroid and kidney cancers. She had also been to hospital 4 times for a collapsed lung. She had no skin lesions and no family history of collapsed lungs or kidney cancer. Genetic testing confirmed the diagnosis of BHD. As well as a mutation in FLCN, a mutation in the gene BRCA2 was also discovered. Mutations in BRCA2 increase the risk of breast and ovarian cancer. After diagnosis she developed further kidney cancers which spread to her liver. In BHD, kidney cancer is normally slow growing and does not spread. She was also diagnosed with breast cancer. This case report highlights the importance of genetic screening and early diagnosis. Knowledge of these mutations allows the individual to get regular screens to check for any cancer. It also allows their family members to be tested and, if necessary, get screened as well.

Case Report 3

This case report featured 3 individuals who were diagnosed with BHD through referral to the dermatology (skin) clinic. The first patient had multiple small, skin-coloured, dome-shaped papules on her face and neck and a family history of colon cancer. A biopsy of the skin lesions was taken, and they were confirmed to be angiofibromas. CT scans showed she had cysts in her lung and kidneys. Genetic testing showed she had 2 different mutations in FLCN, and she was diagnosed with BHD.

To our knowledge, this is the first time 2 different FLCN mutations have been reported in the same individual. We have 2 copies of every gene. A mutation in one copy of FLCN is enough to cause the symptoms seen in BHD.  This patient’s parents are no longer alive, and so it is impossible to tell whether just one or both copies of FLCN are mutated.

The third case described two further patients, a mother and daughter. The mother, a 76-year-old, had widespread skin lesions on her face and previously had colon cancer. The skin lesions were confirmed to be trichodiscomas and genetic testing revealed a mutation in FLCN. Her daughter also had trichodiscomas and a history of collapsed lungs and parotid oncocytoma. She was also diagnosed with BHD after genetic testing showed she had inherited a mutated FLCN gene from her mother.

These case reports all document ‘firsts’ for BHD and expand our knowledge of the condition. Each case is different, yet they all highlight the importance of genetic testing. Genetic testing helps diagnose conditions. Early diagnosis of BHD is important to ensure any kidney cancer is found and treated quickly. Genetic testing ensures the correct diagnosis is made. As shown here, it can also identify other mutations or conditions that might have been missed. We have more information on genetic testing here. You can read our toolkit blog post discussing what to expect when going to a clinical genetics appointment here.

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