BHD in people with Smith-Magenis syndrome
22 Sep 2023
Birt-Hogg-Dubé syndrome (BHD) is characterised by skin lesions, lung cysts, collapsed lungs and an increased risk of kidney cancer. It is associated with changes in the gene folliculin (FLCN). Our genes are organised into thread-like structures called chromosomes. Humans have 23 pairs of chromosomes. The FLCN gene is found on chromosome 17, in a specific region called “17p11.2”. Another condition, called Smith-Magenis syndrome (SMS) is also associated with a deletion of this 17p11.2 region.
Unlike BHD, SMS is not normally inherited and occurs in every 1 in 15,000 – 25,000 people. Individuals with SMS often have a distinct facial appearance and varying degrees of developmental delay and intellectual disability. People with SMS also have distinct behaviours such as sleep disturbance and hyperactivity. However, this condition is distinct from BHD, as this 17p11.2 region also contains a gene called RAI1. Research has shown that a loss of RAI1 is responsible for most of the features seen in SMS. As such, people with BHD do not get the features seen in SMS. However, people with SMS may also be missing a FLCN gene and therefore may be at risk of the features seen in BHD. As the most serious complication of BHD is kidney cancer, people with BHD should get regular scans to monitor their kidneys. So far, cancer has only been occasionally reported in people with SMS and individuals do not have regular kidney scans.
To date, there have only been a few reports of people with SMS having features of BHD. A recent survey*, carried out by PRISMS (Parents and Researchers Interested in Smith-Magenis Syndrome) looked at the prevalence of BHD features in people with SMS. Of 117 respondents, 7 people reported at least one feature of BHD. 5 people had a collapsed lung, and 2 people had fibrofolliculomas. There were no cases of kidney cancer. However, most people in this survey were under 30 years of age. It is thought that the average age of onsent of kidney cancer in people with BHD is 50.
A recent paper* has summarised 4 cases of BHD in people with SMS and provides recommendations for cancer screening. All cases were confirmed to be lacking a copy of the FLCN gene. The first case decribed a patient (aged 50) who was found to have hybrid oncocytic tumours in both their kidneys and underwent surgery to remove these tumours. They did not have any skin lesions or lung cysts. The second patient was diagnosed with SMS aged 37. Aged 45, they were found to have diffuse B cell lymphoma. Scans also showed they had lesions on their kidney and further tests revealed this to be chromophobe kidney cancer. They had no skin or lung features of BHD. The third patient, aged 25, had lung cysts and skin lesions consistent with BHD. They had no kidney tumours. The last patient was aged 42 and had surgery to remove a 3.6 cm tumour that was confirmed to be chromophobe kidney cancer. They had no skin lesions or lung cysts.
In summary, this recent report identified 4 cases of people with SMS who also had features of BHD. 3 of these had kidney tumours. The authors of this study recommend screening for kidney cancer in adults with SMS in line with the current BHD guidelines, where kidney scans are recommended at least every 3 years starting from age 20. Most of the studies in SMS so far have been done in children and adolescents and so it is still unclear how common features of BHD in SMS are, considering the features in BHD typically appear in adulthood. Further work, particularly long-term studies are required to fully characterise BHD in people with SMS.
*Unfortunately these papers are not open access. Please contact if you have any questions.