Smith-Magenis Syndrome (SMS) is a neurodevelopmental condition most commonly caused by a deletion of an area called 17p11.2 on chromosome 17. The gene which predominantly causes the neurodevelopmental symptoms exhibited in SMS is called Retinoic Acid Induced 1 (RAI1), however in most cases of SMS multiple genes on this region of chromosome 17 are affected including Folliculin (FLCN). Variants in Folliculin including deletions cause Birt-Hogg-Dubé syndrome (BHD). Interestingly there have been very few reports of BHD symptoms occurring in SMS. A recent study by Finucane et al., collected data from 117 SMS patients asking if they had any of the three core symptoms associated with BHD: fibrofolliculomas, pneumothorax and kidney cancer. Five people reported pneumothoraces and two reported fibrofolliculoma. Four of the pneumothoraces occurred in childhood, three being under the age of 4. This differs to individuals with BHD syndrome, who most commonly develop their first spontaneous pneumothoraces in their 20’s or 30’s. It must be noted that unexpectedly one of the participants who developed a pneumothorax only had a mutation in their RAI1 gene and not Folliculin . It remains to be determined if this was an unrelated spontaneous event or if there is a relationship between RAI1 and Folliculin.
Although more research is required to fully understand the relationship between BHD and SMS, this study suggests that patients with SMS may be at greater risk of manifesting symptoms of BHD and it is important for families to be aware of the association so that they can recognize symptoms of BHD early.
PRISM is a nonprofit, advocacy, education, and support organization for individuals with SMS and their families. They provide advice on their website regarding BHD and recommendations for kidney screening.