Biallelic germline MUTYH mutations: Skin findings in 9 patients

(Poster reference number 5611)Frederic Caux, MD, PhD, Reference Center for Genetic Skin Diseases, Bobigny,France; Annie Levy, MD, Department of Pathology, Bobigny, France; ChrystelleColas, MD, Laboratory of Oncogenetics, Paris, France; Liliane Laroche, MD, PhD,Department of Dermatology, Bobigny, France; Pierre-Olivier Schischmanoff, PhD,Department of Biochemistry, Bobigny, France

Biallelic germline MUTYHmutations (Me/e) are associated with autosomal recessiveadenomatous polyposis and colorectal cancer. Skin lesions, such as sebaceousadenomas, hyperplasia, or carcinomas, may occur in association. The prevalence ofthese lesions is unknown, because only case reports have been described. In orderto assess prevalence and describe histologically these lesions, we performed asystematic clinical examination of 9 Me/eindividuals. A dermatologic examinationhas been proposed to all Me/e patients seen in oncogenetic counseling (n ¼ 36).Nine patients were examined, including 8 by the same dermatologist. Six skinbiopsies were performed in 4 patients. Colonic manifestations were gathered inorder to search for phenotypeegenotype correlation. There were 5 males and 4females, with a mean age of 49.3 years (range, 26-65). Six out of 9 patients had skinlesions with a mean age of beginning of 43 years (range, 33-54). These lesions wereyellowish papules in a variable number occurring on the face (forehead and cheeks).Analysis of 6 lesions always demonstrated sebaceous hyperplasia, none showingmicrosatellite instability (n ¼ 3). Colonic polyposis was present in 8 patients with amean beginning age of 40.6 years (range, 30-49) and a variable number of polyps(range, 5-150). A colorectal cancer was associated in 6 patients. MUTYH analysisdemonstrated homozygous mutations in 7 patients (p.Gln337Ter, p.Gly382Asp,p.Tyr165Cys, and p.Glu396GlyfsX43) and compound heterozygous mutations in 2patients (p.Tyr165Cys and p.Glu466del; p.Gly382Asp and p.Pro391Leu). Nophenotypeegenotype correlation was detected. Treatment with isotretinoin com-pletely cleared skin lesions (n¼ 3). Prevalence of sebaceous lesions is high (66%) inour Me/e patients. These lesions constantly were hyperplasia while 14 sebaceoustumors (8 adenomas, 4 hyperplasia, and 2 carcinomas) have been described in theliterature. Dermatologic appearance of these patients may evoke MuireTorresyndrome. However, MuireTorre syndrome is autosomal dominant and character-ized by sebaceous adenomas. Skin findings also share similarities with multiplesebaceous hyperplasia seen in transplant recipients under immunosuppressivetherapies. Finally, we observed a high prevalence of sebaceous hyperplasia in Me/e

patients. Dermatologists have to be aware that multiple facial yellowish papules in ayoung individual is not specific of MuireTorre syndrome, but may also lead to searchfor MUTYH mutations and to perform colonoscopy.

AB92

cial support: None identified.

Commer

Birt-Hogg-Dub�e syndrome

(Poster reference number 4844)Anjali Mahto, MBBCh, Watford General Hospital, Watford, United Kingdom;Michele Murdoch, MBBS, Watford General Hospital, Watford, United Kingdom

Background: A 46-year-old woman gave a 3-year history of occasionally itchy spotson the face. Her father and paternal grandmother had similar lesions. She had noprevious history of pneumothorax or renal cancer. There was no family history ofrenal malignancy or pneumothorax. On examination, both the patient and her fatherhadmultiple, small (2-4 mm), dome-shaped, flesh-colored papules affecting the noseand cheeks. The neck, trunk, and oral mucosa were normal.

Investigations: Skin biopsy of a facial papule showed a well-formed hair follicle witha dilated infundibulum containing laminated keratin. There were characteristicanastomosing epithelial strandswithin amantle of loosemucinous connective tissueradiating from the hair follicle epithelium. The findings were consistent with afibrofolliculoma. Genetic testing was subsequently carried out to identify possiblemutations in the folliculin (FLCN) gene. This confirmed the presence of a previouslyunrecognized substitution mutation at position 456 in exon 4 (c.1A[G). Thismutation was carried by the patient, her father, and, on further family studies, alsoher daughter, who has no cutaneous lesions. Based on the combination of clinicalfeatures and FLCN gene mutation in our patient, a diagnosis of Birt-Hogg-Dub�e(BHD) syndrome was made.

Further investigations: Chest radiograph and a computed tomographic scan of thethorax did not show the presence of lung cysts. Renal MRI was normal.

Discussion: BHD syndrome is a rare autosomal dominant genodermatosis that ischaracterized by fibrofolliculomas, lung cysts, spontaneous pneumothorax, andrenal cancer. It is caused by mutations in the FLCN gene found on chromosome17p11.2. The gene encodes a 579eamino acid protein, folliculin, which is highlyconserved among species. Its function is largely unknown, but recent evidencesuggests that it may be involved in the AMPK andmTOR signaling pathways acting asa tumor-suppressor agent. Patients with BHD have a 7-fold increased risk of renalcancer and 50-fold increased risk of spontaneous pneumothorax compared to thegeneral population. It is therefore important to offer genetic testing to familymembers and appropriate clinical surveillance once a diagnosis is made. Our patientand her daughter are currently receiving screening with annual renal MRI. To date,all affected family members remain well and have had no internal malignancies.

cial support: None identified.

Commer

J AM ACAD DERMATOL

Bloom syndrome: Case report

(Poster reference number 5309)Ricardo Villa, MD, BWS, S~ao Paulo, Brazil; Nabil Hamaoui, MD, BWS, S~ao Paulo,Brazil; Valcinir Bedin, MD, BWS, S~ao Paulo, Brazil; Vanessa Moreira, MD, BWS, S~aoPaulo, Brazil

Background: Bloom syndrome is an autosomal recessive disease characterized bysunlight sensitivity, facial telangiectasia, short stature, and a high risk of developingcancer and chromosomal instability. Patients with the syndrome have 150-300 timesmore risk of developing cancer when compared to the general population, andabout a 20% increase in malignancies, including acute leukemia, lymphoma, skincancers, and breast and gastrointestinal cancer. It may be present in moderatemental retardation with learning difficulties, dolicocephalia, microcephaly, narrowface, malar hypoplasia, prominent ears and nose, absence of maxillary lateralincisors, bronchiectasis, chronic pulmonary disease, azoospermia, cryptorchidism,syndactyly, polydactyly, hypo- or hyperpigmented stains, caf�e au lait spots, hyper-trichosis, and diabetes mellitus. It is a rare syndrome; by 2003, approximately 220cases were reported, mostly in Ashkenazi Jews.

Case report: A 27-year-old man came to our service complaining of a painful andbleeding lesion located on lower lip since childhood. During the interview hereferred consanguineous parents. Physical evaluation noticed short stature (130cm), long face, malar hypoplasia, a prominent nose, and low-set ears. Dermatologicevaluation showed crusted ulceration in hemorrhagic bottom on lower lip,hyperchromic brownish macules (caf�e au lait) on the abdomen and sacral regionand hyperchromic and crusted papules on the abdomen and upper limbs. Fromhistory and findings, the suspicious of Bloom syndrome and lip squamous cellcarcinoma was made. Labial biopsy showed epithelial hyperplasia with mild degreeof atypia. Established treatment was chemical cauterization with ATA 15% and lipsunscreen besides recommendation of facial and body photoprotection, informa-tion and guidance about the syndrome. Clinical follow-up due to high risk ofmalignancy is made.

Discussion: Predisposition to an early development of a wide variety of cancers isone of Bloom syndrome’s main characteristics. The identification of the syndrome ismandatory to follow-up and diagnose malignant lesions earlier. Photoprotection isalways necessary because of increased sensitivity to sunlight. This case reportreveals the importance of a holistic look at the patient extrapolating the maincomplain and seeking a detailed history and physical examination

cial support: None identified.

Commer

Carbon dioxide laser ablation followed by photodynamic therapy fornodular basal cell carcinomas in Gorlin syndrome

(Poster reference number 5524)Julieta Spada, MD, Centro de Investigaciones Dermatol�ogicas, Ciudada Aut�onomade Buenos Aires, Argentina; Alejandra Garrido, MD, Centro de InvestigacionesDermatol�ogicas, CABA, Argentina; Edgardo Norberto Chouela, PhD, Centro deInvestigaciones Dermatol�ogicas, CABA, Argentina; Eliana Kos, MD, Centro deInvestigaciones Dermatol�ogicas, CABA, Argentina; Mar�ıa de Los �Angeles Pyke,MD, Centro de Investigaciones Dermatol�ogicas, CABA, Argentina; Mar�ıa GabrielaSpelta, MD, Centro de Investigaciones Dermatol�ogicas, CABA, Argentina; MarianaLequio, Centro de Investigaciones Dermatol�ogicas, CABA, Argentina

Background: Gorlin syndrome (nevoid basal cell carcinoma syndrome) is a geneticdisorder caused by a mutation in the PTCH gene. The inheritance is autosomaldominant in most of the cases, but it can also develop sporadically. This syndromeshows a high penetrance and variable expressiveness and it is characterized by thepresence of multiple pigmented basal cell carcinomas (BCCs), keratocysts in thejaws, palmar and/or plantar pits, and calcification of the falx cerebri, among otheraffections.

Methods: Two patients diagnosed with Gorlin syndromewere included in this study,both with multiple nodular BCCs on their head, neck, and chest. The procedureconsisted on debulking with carbon dioxide (CO2) laser under local infiltrativeanesthesia with lidocaine. The depth of the ablation depended on the level ofinfiltration indicated by histopathology. Immediately after debulking, photodynamictherapy (PDT) was performed using methyl-aminolevulinic acid (MAL) 3 hoursbefore illumination with a 630-nm red light (7 minutes, 37 J/cm2).

Results: Both patients included were treated with CO2 debulking followed by PDTusing methyl- aminolevulinic acid (MAL). The most common adverse effects werelocalized reactions in the treatment area and during illumination, experiencingvarying degree of pain (from none to mild). Overall, tolerance of the procedures wasgood.

Conclusion: Surgical excision and cryotherapy had been used as standard methodsfor the treatment of BCCs in Gorlin syndrome. The results of these techniques oftenimply significant disfigurement and discomfort for patients, as it is a chroniccondition in under which subjects develop new lesions throughout their life. Thetreatment approach should aim to achieve long-term preservation of healthy skin asmuch as possible, particularly when dealing with multiple lesions. CO2 laserablation of BCCs followed by PDT is a therapeutic option that offers good aestheticresults. This fact is particularly important for relatively young patients suffering fromGorlin syndrome.

cial support: None identified.

Commer

APRIL 2012