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Brooke-Spiegler syndrome(SBS; BRSS)

MedGen UID:
346703
Concept ID:
C1857941
Disease or Syndrome
Synonym: Spiegler-Brooke syndrome
SNOMED CT: Brooke-Spiegler syndrome (703531009); Spiegler-Brooke syndrome (703531009)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): CYLD (16q12.1)
 
Monarch Initiative: MONDO:0011512
OMIM®: 605041
Orphanet: ORPHA79493

Disease characteristics

Excerpted from the GeneReview: CYLD Cutaneous Syndrome
CYLD cutaneous syndrome (CCS) typically manifests in the second or third decade with the appearance of multiple skin tumors including cylindromas, spiradenomas, trichoepitheliomas, and rarely, membranous basal cell adenoma of the salivary gland. The first tumor typically develops at puberty and tumors progressively accumulate through adulthood. Females often have more tumors than males. Tumors typically arise on the scalp and face but can also arise on the torso and sun-protected sites, such as the genital and axillary skin. A minority of individuals develop salivary gland tumors. Rarely, pulmonary cylindromas can develop in large airways and compromise breathing. Although the tumors are usually benign, malignant transformation is recognized. [from GeneReviews]
Authors:
Anna Dubois  |  Neil Rajan   view full author information

Additional descriptions

From OMIM
Brooke-Spiegler syndrome (BRSS) is an autosomal dominant disorder classically characterized by the appearance of multiple skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. These tumors are typically located in the head and neck region, appear in early adulthood, and gradually increase in size and number throughout life (Scheinfeld et al., 2003). Because BRSS, familial cylindromatosis, and MFT1 are allelic, and because different manifestations of each have been described within a single family, many consider these disorders to represent a phenotypic spectrum of a single disease entity (Gerretsen et al., 1995; Lee et al., 2005; Bowen et al., 2005; Young et al., 2006; Saggar et al., 2008). Blake and Toro (2009) provided a review of Brooke-Spiegler syndrome and pathogenic mutations in the CYLD gene.  http://www.omim.org/entry/605041
From MedlinePlus Genetics
CYLD cutaneous syndrome is a genetic condition characterized by the growth of multiple noncancerous (benign) skin tumors. These tumors develop from structures associated with the skin (skin appendages), such as hair follicles. More than one type of skin tumor often develops, including benign growths called cylindromas, spiradenomas, and trichoepitheliomas. Cylindromas were previously thought to derive from sweat glands, but they are now generally believed to begin in hair follicles and often appear on the scalp. Spiradenomas are related to cylindromas and it is common to find features of both of these benign growths in a single tumor. Trichoepitheliomas arise from hair follicles and typically develop on the skin around the nose and upper lip.

While the skin tumors associated with CYLD cutaneous syndrome are typically benign, occasionally they may become cancerous (malignant). When becoming malignant, tumors often grow rapidly and become open sores (ulcers). Affected individuals are also at increased risk of developing tumors in structures other than skin; for example benign or malignant tumors of the salivary glands occur in some people with the condition.            

People with CYLD cutaneous syndrome typically begin developing tumors in late childhood or in their teens. For reasons that are unclear, females with CYLD cutaneous syndrome tend to develop more tumors than males with this condition. Tumors tend to grow larger and increase in number over time. Large benign tumors may become ulcers and prone to infections. The tumors are most often found on the head and neck, including the scalp. Tumors that occur in the eyes, ears, nose, or mouth can affect the senses, including vision and hearing. Less frequently, tumors develop on the torso, armpits, or genitals. Genital tumors may cause pain and sexual dysfunction. Rarely, cylindromas develop in the airways and can cause problems with breathing (respiratory insufficiency).

The tumors in CYLD cutaneous syndrome can be disfiguring and may contribute to depression or other psychological problems. 

CYLD cutaneous syndrome includes the conditions previously called Brooke-Spiegler syndrome, multiple familial trichoepithelioma, and familial cylindromatosis. These conditions were once thought to be distinct disorders but are now considered to be the same condition.  https://medlineplus.gov/genetics/condition/cyld-cutaneous-syndrome

Clinical features

From HPO
Neoplasm
MedGen UID:
10294
Concept ID:
C0027651
Neoplastic Process
An organ or organ-system abnormality that consists of uncontrolled autonomous cell-proliferation which can occur in any part of the body as a benign or malignant neoplasm (tumor).
Milia
MedGen UID:
87528
Concept ID:
C0345996
Anatomical Abnormality
Presence of multiple small cysts containing keratin (skin protein) and presenting as tiny pearly-white bumps just under the surface of the skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBrooke-Spiegler syndrome
Follow this link to review classifications for Brooke-Spiegler syndrome in Orphanet.

Professional guidelines

PubMed

Nagy N, Farkas K, Kemény L, Széll M
Eur J Med Genet 2015 May;58(5):271-8. Epub 2015 Mar 14 doi: 10.1016/j.ejmg.2015.02.010. PMID: 25782638
Alessi SS, Sanches JA, Oliveira WR, Messina MC, Pimentel ER, Festa Neto C
Clinics (Sao Paulo) 2009;64(10):961-6. doi: 10.1590/S1807-59322009001000005. PMID: 19841702Free PMC Article
Bowen S, Gill M, Lee DA, Fisher G, Geronemus RG, Vazquez ME, Celebi JT
J Invest Dermatol 2005 May;124(5):919-20. doi: 10.1111/j.0022-202X.2005.23688.x. PMID: 15854031

Suggested Reading

Recent clinical studies

Etiology

Srikantharajah T, Skovby F, Behrendt N, Jemec GBE, Saunte DM
Acta Dermatovenerol Alp Pannonica Adriat 2020 Sep;29(3):133-140. PMID: 32975300
Davies HR, Hodgson K, Schwalbe E, Coxhead J, Sinclair N, Zou X, Cockell S, Husain A, Nik-Zainal S, Rajan N
Nat Commun 2019 Oct 17;10(1):4717. doi: 10.1038/s41467-019-12746-w. PMID: 31624251Free PMC Article
Kacerovska D, Vanecek T, Spagnolo DV, Bisceglia M, Zelger B, Michal M, Kazakov DV
Am J Dermatopathol 2013 Feb;35(1):19-24. doi: 10.1097/DAD.0b013e318255dd37. PMID: 22588548
Ponti G, Nasti S, Losi L, Pastorino L, Pollio A, Benassi L, Giudice S, Bertazzoni G, Veratti E, Azzoni P, Bianchi Scarrà G, Seidenari S
J Cutan Pathol 2012 Mar;39(3):366-71. Epub 2011 Nov 12 doi: 10.1111/j.1600-0560.2011.01813.x. PMID: 22077640
Kazakov DV, Grossmann P, Spagnolo DV, Vanecek T, Vazmitel M, Kacerovska D, Zelger B, Calonje E, Michal M
Am J Dermatopathol 2010 May;32(3):215-221. doi: 10.1097/DAD.0b013e3181b9678c. PMID: 20075707

Diagnosis

Arandia JOA, Magalhães TC, Gomes de Sá GM, Carneiro LH, Ramos-E-Silva M
Skinmed 2023;21(1):47-50. Epub 2023 Mar 29 PMID: 36987829
Nagy N, Farkas K, Kemény L, Széll M
Eur J Med Genet 2015 May;58(5):271-8. Epub 2015 Mar 14 doi: 10.1016/j.ejmg.2015.02.010. PMID: 25782638
Jordão C, de Magalhães TC, Cuzzi T, Ramos-e-Silva M
Int J Dermatol 2015 Mar;54(3):275-8. Epub 2014 Dec 16 doi: 10.1111/ijd.12600. PMID: 25515269
Layegh P, Sharifi-Sistani N, Abadian M, Moghiman T
Indian J Dermatol Venereol Leprol 2008 Nov-Dec;74(6):632-4. doi: 10.4103/0378-6323.45109. PMID: 19171990
Kim C, Kovich OI, Dosik J
Dermatol Online J 2007 Jan 27;13(1):10. PMID: 17511943

Therapy

Botsali A, Caliskan E
An Bras Dermatol 2022 Jul-Aug;97(4):541-543. Epub 2022 May 30 doi: 10.1016/j.abd.2020.12.014. PMID: 35654650Free PMC Article
Hunstig F, Schulz S, Nieten I, Froster U, Boltze C, Schliemann S, Hochhaus A, La Rosée P
J Cancer Res Clin Oncol 2016 Apr;142(4):845-8. Epub 2015 Dec 11 doi: 10.1007/s00432-015-2079-y. PMID: 26660106
Ponti G, Nasti S, Losi L, Pastorino L, Pollio A, Benassi L, Giudice S, Bertazzoni G, Veratti E, Azzoni P, Bianchi Scarrà G, Seidenari S
J Cutan Pathol 2012 Mar;39(3):366-71. Epub 2011 Nov 12 doi: 10.1111/j.1600-0560.2011.01813.x. PMID: 22077640
Kazakov DV, Grossmann P, Spagnolo DV, Vanecek T, Vazmitel M, Kacerovska D, Zelger B, Calonje E, Michal M
Am J Dermatopathol 2010 May;32(3):215-221. doi: 10.1097/DAD.0b013e3181b9678c. PMID: 20075707
Layegh P, Sharifi-Sistani N, Abadian M, Moghiman T
Indian J Dermatol Venereol Leprol 2008 Nov-Dec;74(6):632-4. doi: 10.4103/0378-6323.45109. PMID: 19171990

Prognosis

Danis J, Kelemen E, Rajan N, Nagy N, Széll M, Ádám É
Exp Dermatol 2021 Nov;30(11):1705-1710. Epub 2021 May 17 doi: 10.1111/exd.14365. PMID: 33999445
Srikantharajah T, Skovby F, Behrendt N, Jemec GBE, Saunte DM
Acta Dermatovenerol Alp Pannonica Adriat 2020 Sep;29(3):133-140. PMID: 32975300
Pap ÉM, Farkas K, Széll M, Németh G, Rajan N, Nagy N
Exp Dermatol 2020 Oct;29(10):1017-1020. Epub 2020 Sep 17 doi: 10.1111/exd.14161. PMID: 32744342
Andersson MK, Kölby L, Nilsson JA, Stenman G
J Plast Surg Hand Surg 2019 Apr;53(2):71-75. Epub 2019 Jan 24 doi: 10.1080/2000656X.2018.1547736. PMID: 30676842
Richmond HM, Duvic M, Macfarlane DF
Am J Clin Dermatol 2010;11(4):233-46. doi: 10.2165/11533260-000000000-00000. PMID: 20509718

Clinical prediction guides

Srikantharajah T, Skovby F, Behrendt N, Jemec GBE, Saunte DM
Acta Dermatovenerol Alp Pannonica Adriat 2020 Sep;29(3):133-140. PMID: 32975300
Andersson MK, Kölby L, Nilsson JA, Stenman G
J Plast Surg Hand Surg 2019 Apr;53(2):71-75. Epub 2019 Jan 24 doi: 10.1080/2000656X.2018.1547736. PMID: 30676842
Cüre K, Kocatürk E, Koku Aksu AE, Yüksel T, Leblebici C, Özekinci S, Özkaya Ö, Değirmentepe E
Clin Exp Dermatol 2017 Dec;42(8):906-909. Epub 2017 Oct 4 doi: 10.1111/ced.13223. PMID: 28976013
Nagy N, Farkas K, Kemény L, Széll M
Eur J Med Genet 2015 May;58(5):271-8. Epub 2015 Mar 14 doi: 10.1016/j.ejmg.2015.02.010. PMID: 25782638
Kacerovska D, Vanecek T, Spagnolo DV, Bisceglia M, Zelger B, Michal M, Kazakov DV
Am J Dermatopathol 2013 Feb;35(1):19-24. doi: 10.1097/DAD.0b013e318255dd37. PMID: 22588548

Recent systematic reviews

Singh DD, Naujoks C, Depprich R, Schulte KW, Jankowiak F, Kübler NR, Handschel J
J Craniomaxillofac Surg 2013 Sep;41(6):516-21. Epub 2012 Dec 21 doi: 10.1016/j.jcms.2012.11.016. PMID: 23260808

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