Birt-Hogg-Dube syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: HORNSTEIN-KNICKENBERG SYNDROME
BHD
fibrofolliculomas with trichodiscomas and acrochordons
Number of Symptoms 29
OrphanetNr: 122
OMIM Id: 135150
ICD-10:
UMLs: C0346010
MeSH: D058249
MedDRA: 10067736
Snomed: 110985001

Prevalence, inheritance and age of onset:

Prevalence: 0.5 of 100 000 [Orphanet]
Inheritance: Autosomal dominant
[Orphanet]
Age of onset: Adult
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic skin tumor
 -Rare genetic disease
Inherited renal cell cancer-predisposing syndrome
 -Rare genetic disease
 -Rare oncologic disease
 -Rare renal disease
Rare skin tumor or hamartoma
 -Rare oncologic disease
 -Rare skin disease

Symptom Information: Sort by abundance 

1
(HPO:0000107) Renal cyst 126 / 7739
2
(HPO:0009726) Renal neoplasm Occasional [Orphanet] 20 / 7739
3
(HPO:0005584) Renal cell carcinoma 13 / 7739
4
(HPO:0100684) Salivary gland neoplasm Occasional [Orphanet] 4 / 7739
5
(HPO:0000510) Rod-cone dystrophy Frequent [Orphanet] 266 / 7739
6
(HPO:0100031) Neoplasm of the thyroid gland Occasional [Orphanet] 15 / 7739
7
(HPO:0100733) Neoplasm of the parathyroid gland Occasional [Orphanet] 2 / 7739
8
(HPO:0007378) Neoplasm of the gastrointestinal tract Occasional [Orphanet] 11 / 7739
9
(HPO:0001438) Abnormality of the abdomen 28 / 7739
10
(HPO:0010609) Skin tags Very frequent [Orphanet] 12 / 7739
11
(HPO:0001595) Abnormality of the hair 89 / 7739
12
(HPO:0002097) Emphysema Very frequent [Orphanet] 40 / 7739
13
(HPO:0002108) Spontaneous pneumothorax 3 / 7739
14
(HPO:0002088) Abnormality of lung morphology Frequent [Orphanet] 11 / 7739
15
(HPO:0001012) Multiple lipomas Frequent [Orphanet] 43 / 7739
16
(HPO:0000006) Autosomal dominant inheritance 2518 / 7739
17
(OMIM) Fibrofolliculomas 1 / 7739
18
(OMIM) Parotid oncocytomas 1 / 7739
19
(OMIM) Colonic polyps 1 / 7739
20
(HPO:0030350) Erythematous papule Very frequent [Orphanet] 123 / 7739
21
(OMIM) Facial papules 1 / 7739
22
(OMIM) Colorectal adenomas 3 / 7739
23
(MedDRA:10068749) Lung cyst 3 / 7739
24
(OMIM) Neural tissue tumors 1 / 7739
25
(OMIM) Trichodiscomas (tumor of the hair disc) 1 / 7739
26
(OMIM) Bullous disease 1 / 7739
27
(MedDRA:10000591) Acrochordon 1 / 7739
28
(MedDRA:10048945) Angiolipoma 1 / 7739
29
(HPO:0030436) Fibrofolliculoma 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Birt-Hogg-Dube syndrome is an autosomal dominant genodermatosis characterized by hair follicle hamartomas, kidney tumors, and spontaneous pneumothorax (Nickerson et al., 2002).

BHD is similar to, but histologically and genetically distinct from, familial multiple discoid fibromas (FMDF; ...

Clinical Description OMIM Hornstein and Knickenberg (1975) first described this disorder as 'perifollicular fibromatosis cutis with polyps of the colon' in 2 sibs. Their father was reportedly similarly affected, indicating an inherited condition. The proband was a 47-year-old woman who developed ...
Molecular genetics OMIM By positional cloning, Nickerson et al. (2002) identified a novel gene (FLCN) in this region encoding a protein called folliculin. In several BHD families, they identified protein-truncating mutations in the FLCN gene (607273.0001-607273.0005). Nickerson et al. (2002) stated ...
Diagnosis GeneReviews The three major features of Birt-Hogg-Dubé syndrome (BHDS) are the presence of the following:...
Clinical Description GeneReviews The clinical characteristics of Birt-Hogg-Dubé syndrome (BHDS) include fibrofolliculomas (specific cutaneous lesions), pulmonary cysts/history of pneumothorax, and various types of renal tumors. Disease severity can vary significantly among family members and between families....
Genotype-Phenotype Correlations GeneReviews Genotype-phenotype correlations have been reported; however, whether these manifestations are truly associated with BHDS remains to be determined through larger studies....
Differential Diagnosis GeneReviews Cutaneous lesions. Fibrofolliculomas are rare and specific for Birt-Hogg-Dubé syndrome (BHDS). Because fibrofolliculomas are clinically similar to various cutaneous lesions, histologic diagnosis is required....
Management GeneReviews To establish the extent of disease in an individual diagnosed with Birt-Hogg-Dubé syndrome (BHDS), the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....