[Multiple self-healing squamous epithelioma is an inherited self-healing skin cancer condition]. / Multiple self-healing squamous epithelioma er en arvelig tilstand med selvhelende hudkræft.

Multiple self-healing squamous epithelioma - Ferguson-Smith disease (MSSE) is an autosomal dominant inherited disease with multiple, recurrent, histologically malignant tumours that undergo spontaneous regression. The gene for MSSE has recently been identified as the transforming growth factor-beta receptor 1 (TGFBR1). Although rare, MSSE constitutes an important model of tumour-biology research. The discovery of the genetic background for MSSE paves the way for further elucidating the mechanisms involved in this peculiar self-healing cancer syndrome.

[Two cases of Richner-Hanhart syndrome (oculocutaneous tyrosinemia)]. / To tilfaelde af Richner-Hanharts syndrom (okulokutan tyrosinaemi).

Richner-Hanhart syndrome or oculocutaneous tyrosinemia is characterized by painful palmo-plantar keratoderma, keratitis with photophobia and progressive mental impairment. The syndrome is caused by deficient hepatic tyrosine aminotransferase and is inherited as an autosomal recessive trait. We report a 28 year-old woman with lifelong photophobia, eye pain and painful plantar hyperkeratotic lesions, necessitating use of a wheelchair. A few days after instituting tyrosine lowering therapy, her eye symptoms disappeared and she could walk without pain. Her brother was later diagnosed with the same disease.

Multiple self-healing squamous epithelioma of Ferguson-Smith: observations in a Danish family covering four generations.

Multiple self-healing squamous epithelioma of Ferguson-Smith (MSSE) is a rare autosomal dominantly inherited disease, almost exclusively reported in patients of Scottish origin, with recurrent, histologically malignant tumours that undergo spontaneous regression. We report clinical observations in a Danish family with 11 affected patients, which appears to be the first Scandinavian family published with the disease. Anamnestic data and data concerning age of onset, localization, number of tumours and treatment modalities were collected from the family and from medical records, and all living patients were examined. Detailed clinical findings in 6 patients are described, together with a summary of clinical data from all 11 affected family members. The mean age of onset in the family was 52.6 years (range 30-81 years). A total of 44 tumours, chiefly located in sun-exposed areas, were recorded and the average number of tumours per patient was 4 (range 1-23). 61.4% of the tumours were excised, 31.8% regressed spontaneously without treatment. MSSE may thus also affect patients of non-Scottish origin. The disease severity can vary greatly among patients and the onset can be at an advanced age. MSSE constitutes an important model for research into tumour biology.

Ichthyosis prematurity syndrome: a well-defined congenital ichthyosis subtype.

Ichthyosis prematurity syndrome is a rare syndrome characterized by the clinical triad of premature birth, thick caseous desquamating epidermis, and neonatal asphyxia. We describe two siblings with ichthyosis prematurity syndrome. The index patient was born at gestational week 34. Immediately after birth he developed respiratory distress and needed intubation. Remarkable skin changes were noticed with universal red, edematous and desquamating, spongy skin giving an impression of excessive vernix caseosa. Marked regression of the edema and ichthyotic scaling was observed within a few weeks. The parents recalled that his elder sister had similar but milder skin changes and respiratory distress syndrome at birth. Ichthyosis prematurity syndrome was suggested and the diagnosis supported by electron microscopy of a skin biopsy specimen showing pathognomonic trilamellar membrane aggregations in the stratum corneum and stratum granulosum. Diagnosing this syndrome is important to reassure parents, obstetricians, and pediatricians about its benign course after complications in the perinatal period.

Multiple self-healing squamous epithelioma in different ethnic groups: more than a founder mutation disorder?

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith Disease, is a rare cancer-associated genodermatosis with an autosomal dominant inheritance. Affected patients suffer from recurrent skin lesions, which clinically and histologically resemble keratoacanthomas or well-differentiated squamous cell carcinomas, but which, if left, undergo spontaneous regression, leaving pronounced scarring. The majority of MSSE cases previously described were of Scottish ancestry and all shared the same at-risk haplotype, suggesting that this disorder was caused by a founder mutation. The candidate locus for MSSE lies in a region of <4 cM in chromosome 9q22, between the markers D9S197 and D9S1809. We recently investigated MSSE families of non-Scottish origin. For every patient of these families, we obtained a detailed clinical history, with particular attention to the age of onset, distribution, and clinical course of their skin lesions. Once confirmed that they were really affected by MSSE, we performed haplotype analysis on them and their families. The haplotypes for polymorphic markers segregating with MSSE in non-Scottish and Scottish families differ, suggesting that MSSE is not caused by a founder mutation and might be more common than originally thought.

Pallister-Killian syndrome: Multiband FISH of tetrasomy 12p.

Two patients with mosaicism for tetrasomy 12p are described. One was diagnosed at the age of 14 years with severe mental retardation and other dysmorphologic findings and abnormal skin pigmentation. Chromosome analysis of a blood sample showed a normal female karyotype. A skin biopsy specimen showed mosaicism for a marker chromosome. The other patient was diagnosed prenatally, from a chorionic villus sample, but only in the direct preparation. Mosaicism for a marker chromosome was demonstrated. The ultrasound examination revealed no abnormalities. Multicolor and multiband fluorescence in situ hybridization analyses showed that the marker chromosome was derived from chromosome 12p, which confirmed the diagnosis of Pallister-Killian syndrome in both patients. To our knowledge, this is the first report of the use of these fluorescence in situ hybridization techniques in Pallister-Killian syndrome whereby the nature of the marker chromosome could be confirmed to be derived from chromosome 12p.

Familial and sporadic porphyria cutanea tarda: clinical, biochemical and genetic features with emphasis on iron status.

The manifestation of porphyria cutanea tarda reflects genetic and environmental factors. Mutations in the uroporphyrinogen decarboxylase gene, located at chromosome 1p34, discriminate familial porphyria cutanea tarda from sporadic cases. Furthermore, mutations in the haemochromatosis gene may be involved in the aetiology. In this study 53 unrelated Danish patients with porphyria cutanea tarda were classified according to uroporphyrinogen decarboxylase and haemochromatosis gene mutations and the genotype related to the clinical and biochemical data. Thirteen patients (25%) had familial porphyria cutanea tarda. The results signify the advantage of DNA diagnostics for identification of familial cases, as anamnestic data are doubtful and erythrocyte uroporphyrinogen decarboxylase activity measurements insufficient for correct classification. Eight patients with porphyria cutanea tarda (15%) were homozygous for the haemochromatosis gene C282Y mutation and 8 patients were heterozygous. Patients homozygous for the haemochromatosis related mutation showed biochemical evidence of excessive iron storage as well as increased urine porphyrin excretion levels. This seems to confirm a relationship between porphyria cutanea tarda and haemochromatosis. No differences were found between patients with sporadic and familial porphyria cutanea tarda regarding age of onset, clinical severity, sex distribution, liver function tests and iron storage parameters. However, daily alcohol intake and use of oestrogens were reported more frequently in the group of sporadic patients. It was found that women were over-represented in our study.