The concomitant occurrence of multiple epidermal cysts, osteomas and thyroid gland nodules is not diagnostic for Gardner syndrome in the absence of intestinal polyposis: a clinical and genetic report.

Gardner syndrome, a phenotypic variant of familial adenomatous polyposis, is characterized by the classical clinical triad of skin and soft tissue tumours, osteomas and intestinal polyposis, but disease patterns with pairs of these findings have also been reported. Different mutations in the adenomatous polyposis coli (APC) gene have been shown to be associated with Gardner syndrome disease phenotypes. A 36-year-old patient presented with multiple epidermal cysts on the face, left ear lobe and neck, and the possible diagnosis of Gardner syndrome was based on the additional findings of two classical osteomas in the left radius and ulna and a cold non-malignant nodule of the thyroid gland. Intestinal polyposis was lacking at the time of examination. Major deletions but not microdeletions were excluded by a cytogenetic analysis with 650 chromosomal bands per haploid set. Systematic sequencing of the entire coding region of the APC gene (> 8500 bp) of the patient and five healthy controls was also performed. As a results, new APC gene polymorphisms were identified in exons 13 [A545A (A/G)] and 15 [G1678G (A/G), S1756S (G/T), P1960P (A/G)]. We also detected D1822V (A/T) which has recently been reported to be potentially related to colorectal carcinoma, and genotyped 194 randomly chosen healthy individuals from the Glasgow area for this as well as for the above variants in exons 13 and 15. Interestingly, of the 194 controls, 112 carried the DD (57.7%), 71 the DV (36.6%), and the remaining 11 (5.7%), including our patient, the VV genotype. It is therefore unlikely that APC D1822V serves as an important marker for colorectal carcinoma. In conclusion, we failed to identify obvious germline candidate mutations in > 8500 bp of the coding region of the APC gene in a patient with multiple epidermal cysts, osteomas and a thyroid gland nodule; major chromosomal deletions were excluded. Therefore, we assume that only the presence of intestinal polyposis is a marker for Gardner syndrome.

Adamantiades-Behçet's disease with inner ear involvement.

Adamantiades-Behçet's disease is a chronic recurrent inflammatory disorder involving the small and large vessels. Typical loci of manifestations are the mucous membranes, skin and eyes, as well as the joints and central nervous system. Other organs are not commonly involved. We present two patients, one with ocular and the other with mucocutaneous manifestation of Adamantiades-Behçet's disease. In addition, the first patient reported three episodes of sudden hearing loss while under immunosuppressive therapy for his eye involvement. The second, therapy-naive patient complained of tinnitus in his left ear. Careful examination revealed vestibular involvement in the first patient and retrocochlear involvement in the second. Inner ear involvement is an uncommon manifestation of Adamantiades-Behçet's disease. In case of relevant signs or history, such as hearing disturbance, tinnitus and/or vertigo, patients should be examined for inner ear involvement.

Mycophenolate mofetil is ineffective in the treatment of mucocutaneous Adamantiades-Behçet's disease.

BACKGROUND: Cyclosporine A and azathioprine are effective on mucocutaneous lesions in Adamantiades-Behçet's disease. Mycophenolate mofetil (MMF) is a drug resembling their activity but with comparably negligible adverse reactions. OBJECTIVE: A prospective clinical proof-of-principle study was conducted to investigate the effectiveness and toxicity of MMF in mucocutaneous Adamantiades-Behçet's disease. METHODS: Thirty patients were to be treated with MMF 2 g/day p.o. for 6 months, in combination with prednisolone 30 mg/day p.o. during the first month of treatment. Inefficacy was followed by an increase in MMF dose to 3 g/day. The primary efficacy variable was the decrease in the disease activity index (DAI) according to a modified variant of the Iran Behçet's Disease Dynamic Activity Measure system. RESULTS: The study was interrupted due to inefficacy of the compound after the intermediate evaluation of the first 6 patients (aged 37.0 +/- 7.7 years with disease duration of 10.0 +/- 8.9 years) as required by the ethical committee. Although an improvement of the DAI from 5.2 +/- 3.5 to 1.3 +/- 0.5 was found after the first month of combination treatment, withdrawal of prednisolone led to quick relapses with a new index increase (3.0 +/- 3.5). The treatment was discontinued in 3 patients after 3 months, in 2 patients after 4 months and in another one after 5 months due to deterioration of the disease. Introduction of interferon alpha(2a) (3 x 9 million IU 3x/week s.c.) in 3 patients decreased the activity index from 4.0 +/- 1.0 to 0.0 +/- 0.0. No adverse effects were detected under MMF treatment. CONCLUSION: MMF (2-3 g/day) is unable to control the signs of mucocutaneous Adamantiades-Behçet's disease.

Multiple familial cutaneous glomangioma: a pedigree of 4 generations and critical analysis of histologic and genetic differences of glomus tumors.

BACKGROUND: Glomangiomas are benign tumors arising from neuromyoarterial cells surrounding cutaneous arteriovenous anastomoses that serve as temperature regulators. They exist as solitary or multiple types, occurring sporadically or in a familial pattern, the latter of which is rare. OBJECTIVE: We describe a 4-generation pedigree of familial cutaneous glomangioma, in addition to the 3 other well-documented pedigrees reported in the literature to date, and we clarify ways in which to distinguish the different types of glomus tumors. METHODS: Nodular skin lesions of 4 affected family members were analyzed by histologic, immunohistologic, and electron microscopic methods. To elucidate the gene defect in this family, we searched for a linkage to a candidate locus on chromosome 11q23 previously identified in paragangliomas, one form of glomus tumor, in 16 family members of 4 generations by using polymorphic markers. RESULTS: The diagnosis of disseminated cutaneous glomangiomas was confirmed histologically in 4 family members of 3 different generations. Glomangiomas were transmitted in an autosomal dominant pattern via the paternal line. Genetic linkage analysis of the affected family members excluded linkage to chromosome 11q23. CONCLUSION: An autosomal dominant pattern of inheritance has been described for glomus tumors of the paraganglioma type originating from the APUD cell system, the underlying genetic defect of which has been mapped to chromosome 11q23. In contrast, we show that the genetic defect in disseminated cutaneous glomus tumors of the glomangioma type deriving from smooth muscle cells or pericytes is not linked to chromosome 11. Thus we suggest that the common term glomus tumor, used for both paragangliomas and glomangiomas in the current literature, is misleading and should be avoided because these tumors have different histologic derivation and genetic origin.

The SAHA syndrome.

The presence of seborrhoea, acne, hirsutism and alopecia in women has first been summarized as SAHA syndrome in 1982 and can be associated with polycystic ovary syndrome, cystic mastitis, obesity and infertility. In 1994, the association of these androgen-dependent cutaneous signs, was classified according to their etiology into four types: (1) idiopathic, (2) ovarian, (3) adrenal, and (4) hyperprolactinemic SAHA. The HAIRAN syndrome has been currently described as a fifth variant with polyendocrinopathy. The SAHA syndrome generally occurs in young to middle-aged women and involves either the presence of elevated blood levels of androgens or increased androgen-driven peripheral response with normal circulating androgen levels. Peripheral metabolism of androgens takes place in various areas within the pilosebaceous unit, as indicated by local differences in the activities of aromatase, 5alpha-reductase as well as of the presence of the androgen receptors. In cases of SAHA syndrome, careful diagnostic and clinical evaluation has to be performed in order to identify the cause for peripheral hyperandrogenism and to exclude androgen-producing tumors. Treatment will target the etiology, whereas the management in idiopathic cases will aim to improve the clinical features of SAHA.