D. Teillac

Localization of the Netherton Syndrome Gene to Chromosome 5q32, by Linkage Analysis and Homozygosity Mapping

Netherton syndrome (NS [MIM 256500]) is a rare and severe autosomal recessive disorder characterized by congenital ichthyosis, a specific hair-shaft defect (trichorrhexis invaginata), and atopic manifestations. Infants with this syndrome often fail to thrive; life-threatening complications result in high postnatal mortality. We report the assignment of the NS gene to chromosome 5q32, by linkage analysis and homozygosity mapping in 20 families affected with NS. Significant evidence for linkage (maximum multipoint LOD score 10.11) between markers D5S2017 and D5S413 was obtained, with no evidence for locus heterogeneity. Analysis of critical recombinants mapped the NS locus between markers D5S463 and D5S2013, within an <3.5-cM genetic interval. The NS locus is telomeric to the cytokine gene cluster in 5q31. The five known genes encoding casein kinase Ialpha, the alpha subunit of retinal rod cGMP phosphodiesterase, the regulator of mitotic-spindle assembly, adrenergic receptor beta2, and the diastrophic dysplasia sulfate-transporter gene, as well as the 38 expressed-sequence tags mapped within the critical region, are not obvious candidates. Our study is the first step toward the positional cloning of the NS gene. This finding promises a better understanding of the molecular mechanisms that control epidermal differentiation and immunity.

Neonatal and Early Infantile Cutaneous Langerhans Cell Histiocytosis: Comparison of Self-regressive and Non–Self-regressive Forms

OBJECTIVES To describe clinical and immunohistochemical findings in patients with cutaneous Langerhans cell histiocytosis (LCH) beginning in the first 3 months of life and to define predictors of disease evolution. DESIGN Observational retrospective survey from July 15, 1989, to April 30, 2007. SETTING Referral center in pediatric dermatology. PATIENTS Thirty-one patients with a diagnosis of cutaneous LCH in the first 3 months of life and no previous visceral LCH. MAIN OUTCOME MEASURES Cutaneous lesion characteristics, regulatory T-lymphocyte density, and E-cadherin expression were assessed. Data were compared between the patient groups with self-regressive vs non-self-regressive forms of cutaneous LCH. Pathologic analysis was performed blinded to patient group. RESULTS Self-regressive cutaneous LCH was found in 21 patients and non-self-regressive cutaneous LCH in 10 patients. Monolesional forms, necrotic lesions, hypopigmented macules at presentation, and distal topography of limb lesions were seen only in patients with self-regressive cutaneous LCH. Regulatory T-lymphocyte density correlated with interleukin 10 expression in lesions (r = 0.77, P = .003) but was not predictive of disease evolution. E-cadherin expression by Langerhans cells was found in 7 patients with disease limited to the skin whether self-regressive or not. One patient with secondary disseminated disease showed loss of E-cadherin expression in Langerhans cells. CONCLUSIONS Some morphologic traits of skin lesions can orient the diagnosis to a self-regressive form of cutaneous LCH. Regulatory T-lymphocyte density does not seem to be predictive of disease evolution. E-cadherin expression seems to be an indicator of limited skin disease but not of disease regression. Additional immunohistochemical study is required to confirm these data.

Intracranial venous anomalies associated with atretic cephalocoeles

Background. Midline scalp lesions are frequent in children. They include soft-tissue masses and atretic meningocoeles. Their recognition is important as their treatment differs. Intracranial venous anomalies are known to be associated with atretic cephalocoeles.¶Materials and methods. A retrospective study was undertaken to assess the frequency of intracranial venous anomalies associated with atretic meningocoeles (AT). Thirty-one patients with AT were studied by MRI. There were 13 meningocoeles and 14 encephalocoeles; 4 have not yet received surgery.¶Results. Venous anomalies were found when the cephalocoeles lay above the torcular. They include absence of the straight sinus and duplication of the longitudinal sinus.¶Conclusion. Venous anomalies are frequent in atretic cephalocoeles and are part of the dysraphic state.

Nutritional outcome in children with severe generalized recessive dystrophic epidermolysis bullosa: a short- and long-term evaluation of gastrostomy and enteral feeding

Background  Generalized recessive dystrophic epidermolysis bullosa (RDEB) is often complicated by high nutritional difficulties with risks of malnutrition.

Treatment of severe alopecia areata by topical applications of cyclosporin A: comparative trial versus placebo in 43 patients

Forty-three patients with severe alopecia areata were divided into two groups: group 1 (n = 22) treated with once-daily application of 0.5 ml of an oily solution containing 100 mg/ml of cyclosporin A (CyA) to one half of the scalp during 6 months; group 2 (n = 21): once-daily application of an oily solution without CyA to one half of the scalp. The development of terminal hairs, generally in the form of small tufts 0.5 to 2 cm in diameter was observed in seven patients in group 1 and not in group 2. No cases of complete hair regrowth were observed. Diffuse vellus hair predominant on the treated side was observed in five patients in group 1 and in three patients in group 2. The local tolerance was good. A few episodes of transient folliculitis (four cases in each group) were noted. The laboratory survey (serum electrolytes, creatinine, uric acid) did not reveal any significant variations and cyclosporin blood levels were always below detectable limits. CyA has never been used topically in man prior to this trial. This comparative trial demonstrated a difference between the two groups, as terminal hairs were observed in seven cases in group 1. This regrowth was mild, of delayed onset and never complete. However, the development of terminal hairs in the treated group suggests a local action of CyA and encourages further therapeutic trials with different concentrations and different vehicles.