# Birt-Hogg-Dubé syndrome: A case series highlighting pulmonary manifestations, rare renal involvement and role of familial diagnosis

## TL;DR

This case series describes three patients with Birt-Hogg-Dubé syndrome, highlighting varied symptoms like lung cysts and rare kidney issues, and the importance of family history in diagnosis.

## Contribution

The study emphasizes the variable clinical presentation of BHDS and the importance of familial evaluation for accurate diagnosis.

## Key findings

- Three patients from the same family showed different BHDS symptoms, including lung cysts and rare kidney tumors.
- Family history played a key role in diagnosing BHDS, especially with repeated pneumothorax and renal cysts.
- All patients tested positive for the FLCN gene mutation, confirming the genetic basis of the syndrome.

## Abstract

ABSTRACT

Birt-Hogg-Dubé syndrome: A case series highlighting pulmonary
manifestations, rare renal involvement and role of familial diagnosis

Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant disease
characterized by cutaneous lesions and renal tumors, along with the presence
of pulmonary cysts. In most cases, it is caused by a mutation in the folliculin
(FLCN) gene. While normally evaluated as a triad, the isolated pulmonary
presentation can still be expected, and repeated pneumothorax history should
be evaluated for BHDS, especially if it is present in family members. In this
case series, three patients with different clinical findings were reported. The
first patient had a repeated pneumothorax history, along with angiomyolipoma,
a relatively unexpected presentation of renal BHDS involvement. The
incidental presence of pneumothorax in his mother had strengthened the
diagnosis of BHDS, for which she also had renal cysts and additional
cutaneous lesions. While these two patients were evaluated on an inpatient
basis, the third patient, the son of the first patient, had been evaluated for
BHDS presence, and pneumothorax, along with pulmonary cysts, was
observed. All three patients were then later referred to a genetic center for
confirmation of the FLCN mutation and tested positive for it. These case series
illustrate the possibility of a different clinical presentation within the same
family and at different ages, along with rare renal presentation and the
possible asymptomatic indolent nature of the disease.

Key words:

Angiomyolipoma; autosomal dominant; Birt-Hogg-Dube
syndrome; folliculin

ÖZ

Birt-Hogg-Dubé sendromu: Pulmoner semptomları, nadir böbrek tutulumunu ve ailesel geçisin rolünü vurgulayan bir vaka serisi

Birt-Hogg-Dubé sendromu (BHDS), pulmoner kistlerin varlığı ile birlikte kutanöz lezyonlar ve böbrek tümörleri ile karakterize nadir
otozomal dominant bir hastalıktır. Çoğu vakada, bu duruma folikülin (FLCN) genindeki bir mutasyon neden olur. Normalde bir triad
olarak değerlendirilse de izole akciğer tutulumu görülebilir ve tekrarlayan pnömotoraks öyküsü, özellikle aile bireylerinde de benzeri
klinik mevcutsa hasta BHDS açısından değerlendirilmelidir. Bu olgu serisinde farklı klinik bulgulara sahip üç hasta sunulmaktadır. İlk
hastada, böbrek BHDS tutulumunun nispeten beklenmedik bir sunumu olan anjiyomiyolipomun yanı sıra tekrarlayan bir pnömotoraks
öyküsü vardı. Annesinde tesadüfen pnömotoraks görülmesi, annede böbrek kistleri ve ek deri lezyonlarının da bulunması ile BHDS
tanısını güçlendirmişti. Bu iki hastaya ek olarak, birinci hastanın oğlu olan üçüncü hastada BHDS için yapılan değerlendirilmede
akciğer kistlerinin yanı sıra pnömotoraks da gözlendi. Daha sonra üç hasta da FLCN mutasyonunun doğrulanması için genetik
merkeze yönlendirildi ve test sonuçları pozitif çıktı. Bu vaka serileri, aynı aile içinde ve farklı yaşlarda farklı klinik belirtilerin ortaya
çıkma olasılığının yanı sıra, nadir görülen böbrek belirtilerini ve hastalığın olası asemptomatik yavaş seyrini göstermektedir.

Anahtar kelimeler:

Anjiyomiyolipom; otosomal dominant; Birt-Hogg-Dube sendromu; folikülin