Clinical research

To date, around 500 families have been reported to have BHD (Published BHD Families). However, BHD syndrome is believed to be under-diagnosed; partly because it is so rare that doctors are often unfamiliar with it, and partly because its phenotypic variation can make it difficult to identify (Menko et al., 2009). For example, Kunogi et al. (2010) sequenced the FLCN gene in 36 patients who presented with multiple lung cysts of unknown cause, and found that 25 carried FLCN mutations. Of these 25 individuals, 21 only displayed pulmonary symptoms at the time of the study (Kunogi et al., 2010). Thus, although these individuals do have BHD, the lack of skin lesions or renal disease makes it difficult to clinically diagnose these patients. Additionally, a recent report described the case of an individual with all three manifestations of BHD, but who had a de novo FLCN mutation, suggesting that a diagnosis of BHD should be considered for patients with one or more of the syndrome’s symptoms, even in the absence of a family history (Menko et al., 2013).

Collating epidemiogical data from different studies into a central database would help to ascertain the true prevalence of BHD syndrome. This research would help to identify any genotype-phenotype correlation, population differences, or genetic modifiers that may not be obvious in individual cohorts. More knowledge about the epidemiology of BHD syndrome would help with the genetic counselling and management of patients, and may also lead to the development of stratified treatments for patients with BHD syndrome.