Three novel point mutations in the keratinocyte transglutaminase (TGK) gene in lamellar ichthyosis: significance for mutant transcript level, TGK immunodetection and activity.

We have investigated 8 patients from 7 unrelated families with lamellar ichthyosis (LI) for defects in the keratinocyte transglutaminase (TGK) gene. We have characterized three novel homozygous mutations and a previously reported splice acceptor site mutation. One patient showed a C-to-T change in the binding site for the transcription factor Sp1 within the promoter region. Another patient had a Gly 143-to-Glu mutation in exon 3 and a third patient, affected with a particular form of LI sparing the four limbs, demonstrated a Val382-to-Met mutation within exon 7. These three patients exhibited drastically reduced transglutaminase activity and an absence of detectable TGK polypeptide, as assessed by immunofluorescence and immunoblotting. Northern blot analysis showed that the Sp1 site mutation was associated with profound reduction of TGK transcript levels whereas normal transcript levels were observed for the two missense mutations. We hypothesize that the Sp1 site mutation impairs transcription of the TGK gene, whereas the two missense mutations induce structural changes leading to protein instability. Linkage to TGK was excluded in another family and no evidence for TGK defect was found in 3 other patients. These results further support the involvement of TGK in some patients with LI. They identify a TGK mutation as a cause for non-generalized LI and further delineate the molecular mechanisms underlying TGK deficiency in LI.

Neonatal and infantile erythrodermas: a retrospective study of 51 patients.

OBJECTIVE: To determine the frequency of the various underlying causes of erythroderma in newborns or infants, as well as which clinical or laboratory findings were relevant for the etiological diagnosis. PATIENTS: Fifty-one patients who presented with exfoliative erythroderma during their first year of life were included in this retrospective study. SETTING: Department of Pediatric Dermatology at a university hospital. RESULTS: On average, the etiological diagnosis was established 11 months after the onset of erythroderma. The underlying causes observed included immunodeficiency (30%), simple or complex ichthyosis (24%), Netherton syndrome (18%), and eczematous or papulosquamous dermatitis (20%). Five patients (10%) had erythroderma of unknown origin. The following parameters were of value in determining the underlying cause of erythroderma: congenital onset, skin induration and the presence of large scaling plaques, alopecia with or without hair dysplasia, evolution, response to topical corticosteroid therapy, presence of infections, and failure to thrive. Histological analysis confirmed the diagnosis in only 19 (45%) of 42 cases. However, it proved of great value for the detection of significant lymphocyte infiltration or keratinocyte necrosis indicating a diagnosis of Omenn syndrome or immunodeficiency. The prognosis was poor in this series: the mortality rate was 16%, and severe dermatosis persisted in 29 (67%) of the survivors. CONCLUSIONS: The etiological diagnosis of neonatal erythroderma is difficult to make; some clinical features may be helpful, but no one feature is characteristic of a cause. An immunodeficiency must be suspected in cases of severe erythroderma with skin induration, severe alopecia, failure to thrive, infectious complications, or evocative histological findings. The prognosis is poor, with a high rate of mortality in immunodeficiency disorders and severe chronic disease in Netherton syndrome and psoriasis.

[Treatment of atopic dermatitis]. / Traitement de la dermatite atopique.

There are three components in the treatment of atopic dermatitis: 1) a general treatment (mainly antibiotherapy directed towards Staphylococcus aureus during acute phases), 2) local treatment (local antiseptics, local steroids, emollients), 3) practical advice. In addition, it is of great importance that clear and complete information on the illness should be given to the parents.

[Dermatitis herpetiformis occuring in patients with celiac disease in childhood]. / Dermatite herpétiforme survenant chez des patients atteints de maladie coeliaque dans l'enfance.

BACKGROUND: Dermatitis herpetiformis (DH) is a chronic papulovesicular immune-mediated disorder associated with gluten-sensitive enteropathy. We report eight cases in which DH appeared many years after celiac disease (CD) in child. PATIENTS AND METHODS: The diagnosis of CD was based on histological features of total or subtotal villous atrophy, full remission after withdrawal of gluten from the diet, and eventually circulating antibodies (IgA gliadin, antireticulin and antiendomysium) at the time of diagnosis and their disappearance under gluten-free diet. The diagnosis of DH was made from clinical findings, histological examination of the involved skin and direct immunofluorescence microscopy of normal or perilesional skin. HLA class II typing was performed in five patients. DRB1, DQA1, DQB1 and DBP1 alleles were studied. RESULTS: DH appeared between 3 and 22 years after the initial diagnosis of CD. Five patients did not show at that time any digestive symptoms. In three cases, a break in the gluten-free diet or a recent revival of the normal diet preceded the rash. In only one case, DH appeared while the patient was under gluten-free diet. In three patients, the rash appeared many years after the gluten-free diet had been stopped. Phenotype DR3 and/or DR7 of the celiac disease could be found in four of the five patients studied; three of them were found to bear DQW2. The DR2 allele was not found in any of the five tested patients. DISCUSSION: These eight cases illustrate the absence of precise nosological barrier between gluten-sensitive enteropathy of the DH and that observed in CD. The presence of the DR7 allele, and especially the absence of the DR2 allele, could explain the particularly severe and symptomatic course of the enteropathy in these patients. The delay in the appearance of DH, after a very variable period of normal diet, could correspond to the necessary time for progressive accumulation of IgA (or immune complex IgA-gluten) in the skin after a digestive sensitization to gluten. The preventive role of gluten-free diet is thus probable. CONCLUSION: CD and DH likely correspond to two different stages of the same disease, thus requiring a prolonged follow-up of both digestive and skin tissues. Long-term eviction of gluten to prevent eventual DH must be balanced with the demand and the cost of such a diet.

[Neurofibromatosis 1: recommendations for management]. / Neurofibromatose 1: recommandations de prise en charge.

Twenty experts, members of a French medical network devoted to neurofibromatosis 1 have elaborated recommendations for the management of the disease. Bibliography was obtained through a Medline of articles from 1966 to 1999 for the terms neurofibromatosis, NF1, neurofibroma and from textbooks. A consensual document was written taking into account extracted data. An annual careful clinical examination is recommended except in cases with complications. Screening investigations are not recommended due to the rarity of complications, generally symptomatic and easily detected during the clinical follow-up. The only controversial exception might be magnetic resonance imaging for early detection of optic pathway gliomas in young children. A co-ordinated follow-up in specialised multidisciplinary centres, providing patients with a rational management, is recommended.

[Cutaneous granulomatous lesions in congenital immune deficiencies. 5 cases]. / Lésions granulomateuses cutanées au cours des déficits immunitaires congénitaux. Cinq observations.

INTRODUCTION: Cutaneous granulomatous lesions rarely occur in primary immunodeficiency syndromes. CASES REPORTS: We observed chronic granulomatous lesions on the skin of 5 children with inborn immunodeficiency syndromes. The deficiency was of the mixed type in all 5 cases and included major hypogammaglobulinaemia in 4. Erythemato-squamous infiltrated plaques were found in 4 children and erythematous nodules in the fifth. Extra-cutaneous lesions (cavum and rectocolon) occurred in 2 children. Search for an infectious cause was negative. Anti-tuberculosis drugs were tried in 3 children as a test regimen and were ineffective. Systemic corticosteroids gave major clinical improvement in 2 children. DISCUSSION: Several pathogenic processes have been hypothesized to explain the development of granulomatous lesions in immunodeficiency syndromes. The action of an unknown infectious agent has been suspected. An intrinsic anomaly in immune function regulation, particularly in a disequilibrium in the complex cytokine network controlling the formation of granulomas could also be involved. Systemic corticosteroid therapy appears to be effective but must be given with caution in these patients with immune deficiency.

[Ultrastructural study of hereditary benign telangiectasia. Differential diagnosis from Osler Rendu disease]. / Etude ultrastructurale des télangiectasies héréditaires bénignes. Un diagnostic différentiel de la maladie de Rendu-Osler.

INTRODUCTION: There are two hereditary forms of primary telangiectasia with a totally opposite prognosis. In Rendu-Osler disease, also called hereditary haemorrhagic telangiectasia, there is a major risk of severe haemorrhage in adults. In benign hereditary telangiectasia there is no such risk. CASE REPORT: We report two brothers who were diagnosed as having Rendu-Osler disease. Under standard electron microscopy, a biopsy of a telangiectasia taken from the right arm pit showed that the vessels of the superficial reticular derma were dilated with thick walls but no dehiscences as in Rendu-Osler disease. DISCUSSION: This ultrastructure explains why there had been no haemorrhages in our two cases and favoured a diagnosis of hereditary benign telangiectasia.

[Giant congenital blue nevus of the scalp]. / Naevus blue géant congénital de l'extrémité cervico-céphalique.

INTRODUCTION: Blue nevi are small acquired melanocytic tumors. Two clinical forms are described, a fibrous form and a cellular form. Giant nevi are exceptional. CASE REPORT: We describe a patient with a giant blue nevus of the scalp. In addition to this congenital, noninvasive tumor the patient presented numerous cutaneous melanocytic nevi. The main lesion was removed by surgical exeresis followed later with reconstruction plasty. The histological examination of the surgical specimen showed an infiltrating blue cell nevi. After a 4-year follow-up, there has been no recurrence and no metastasis. DISCUSSION: There have been 11 cases of giant blue nevi reported in the literature. All were congenital lesions with polymorphous clinical and histological aspects. Fibrous forms are noninvasive and cellular forms have a potential for local invasion, whether shortly after birth or later with invasion of muscles, bone and meninges without intracerebral extension. Congenital blue nevi require early surgical exeresis.

[Rothmund-Thomson syndrome with reduced DNA repair capacity]. / Syndrome de Rothmund-Thomson avec anomalie de l'excision-réparation de l'ADN.

INTRODUCTION: Rothmund-Thomson syndrome is a genodermatosis associated with early poikilodermal lesions. The condition usually occurs in children. Features include skeletal deformations and increased risk of malignancy. CASE REPORT: A 3 and a half year-old girl with poikilodermal lesions predominating in photoexposed areas presented a rash after exposure to sun. The first manifestations occurred during the first months of life. Examination of DNA repair on a culture of UV irradiated fibroblasts showed reduced DNA repair capacity. DISCUSSION: Other childhood photodermatoses were eliminated by the clinical signs. It would be important to know whether there is a correlation between DNA repair and development of neoplasia in Rothmund-Thomson syndrome.

[The importance of early surgery in preventing the esthetic sequelae of cervicofacial mucocutaneous hemangiomas in children]. / Intérêt de la chirurgie précoce dans la prévention des séquelles esthétiques des hémangiomes cutanéo-muqueux cervico-faciaux de l'enfant.

Infants with cutaneous hemangiomas are classically managed medically, well-defined surgery being planned for esthetic correction at the age of 8 to 10 years. We present a series of 65 cases of early surgery in children with head and neck cutaneous or mucosal hemangiomas where irreversible and unesthetic scars were predictable. The surgical procedure was simple and the cosmetic result was better than could be expected after late surgery, limiting psychological consequences. In our opinion, the abstention rule should be changed. A multidisciplinary check-up at 2 years to identify cases with a predictably unesthetic scar after complete resolution of the angioma would help select cases where early surgical correction, taking advantage of the exceptional quality of skin in these young children, would be most beneficial.

[Use of iterative expansion in the early surgical treatment of complex nevi of the head in children]. / Utilisation des expansions itératives dans le traitement chirurgical précoce des naevus complexes céphaliques de l'enfant.

Extensive of congenital pigmented nevi to the face in an infant is an indication for early exeresis to prevent the risk of degeneration. Search for the best esthetic result has led many authors to healthy skin to a maximum, often relying on tissue expansion. The aim of this study was to present the combination of two expansion techniques, prosthetic expansion and differed natural expansion. Five infants with congenital pigmentary nevi extending to more than 50% of a facial anatomic unit were treated. Total treatment was achieved in all patients with three or four procedures. By combining different expansion techniques early treatment can be proposed with good esthetic results and moderate cost.