Expanding the Genotype of Sjögren-Larsson Syndrome: A New Case Due to Two Novel Mutations / Ampliando el genotipo del síndrome de Sjögren-Larsson: un nuevo caso causado por dos nuevas mutaciones

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Skin disorders in the neonatal intensive care unit of a central hospital.

Cutaneous abnormalities in the newborn are usually benign and transitory. However, they may sometimes be extremely distressing both for parents and the medical staff, presenting with significant morbidity and mortality. The aim of this study was to access the clinical features of different skin disorders in a series of newborns, at a level III neonatal intensive care unit (NICU) in the Northern Region of Portugal, and review some of the most impressive cases. Between January 1997 and December 2010, 27 patients were found to have an important cutaneous condition that required admission to the NICU. The most frequent presentations were vesicles and pustules (n=8; 29.6%), followed by erythroderma (n=7; 25.9%), atrophic (n=5; 18.5%) and vascular lesions (n=4; 14.8%). Four (14.8%) patients died in the neonatal period, and further 4 afterwards. Genetic studies, when available, revealed three chromosomal disorders and 6 gene mutations. Overall, skin disorders were not a leading cause of NICU admission (0.43%), but were associated with significant morbidity and mortality.

[Another indication for (erythro)keratodermia variabilis in livestock in the case of a neonatal lamb]. / Ein weiterer Hinweis auf (Erythro)keratodermia variabilis bei Nutztieren am Beispiel eines Schaflammes.

From skin biopsies of a neonatal lamb a congenital skin disease (erythro)keratodermia variabilis was diagnosed which especially showed besides an erythema formation a hyperkeratosis at some wound areas of the body. Despite of a sudden induced intensive therapy the lamb died. At the dissection of the carcass there were no further postmortem-findings which refer to another organic disease than the one of the skin. This case report is the second description of (erythro)keratodermia variabilis in domestic mammals, which is caused by an autosomal dominant inherited horning defect in humans.

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.

Strong founder effect for a transglutaminase 1 gene mutation in lamellar ichthyosis and congenital ichthyosiform erythroderma from Norway.

Autosomal recessive congenital ichthyosis (ARCI) is a clinically heterogeneous disorder of keratinisation. It was recently shown that mutations in the transglutaminase 1 (TGM1) gene may be associated with the clinical subtypes lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (CIE). Thirty-six Norwegian families with LI and seven with non-bullous CIE were studied with microsatellite markers linked to the TGMI gene. One common haplotype for two markers was found on 74% of disease associated chromosomes. Three individuals homozygous for the common haplotype, two affected by LI and one affected by CIE, were analysed for mutations in the TGM1 gene. All three patients were found homozygous for a single A to G transition located in the canonical splice acceptor site of intron 5. Probands from the remaining 40 families with LI and CIE were screened for this mutation and the A to G transition was found on 61 out of 72 alleles associated with LI and on 9 out of 15 alleles associated with CIE. These findings suggest a single founder mutation for the majority of patients with LI and CIE in Norway. The 2526A-->G mutation results in the insertion of a guanosine at position 877 (876insG) in the mature cDNA and the frame shift creates a premature termination at codon 293. The mutation was previously observed in one family with a resulting cDNA that included the entire intron 5. These results suggest that the mutation can result in variant transcripts in different individuals.

Congenital psoriasiform erythrokeratodermia with cleidocranial dysplasia, urogenital anomalies and atresia ani.

We describe two siblings with unique psoriasiform erythrokeratodermia associated with cleidocranial dysplasia, urogenital anomalies and atresia ani. The skin lesions were characterized by demarcated psoriasiform erythema with scaling. A skin biopsy revealed small abscesses containing polymorphonuclear leukocytes in the parakeratotic horny layer, elongation of the rete ridges and dermal papillae, and other findings consistent with psoriasis. A reverse-transcription polymerase chain reaction analysis disclosed increased expression of transforming growth factor alpha in the affected skin lesion of one of the siblings as well as in the skin of a patient with psoriasis. It is suggested that these cases are a variant of a congenital form of psoriasiform erythrokeratodermia.

Netherton's syndrome: a severe neonatal disease. A case report.

A male infant was born with generalized erythroderma and scaling; the newborn demonstrated poor neonatal development and developed several complications such as hypernatremic dehydration, septicemia, gastroenteritis and seizures. In the neonatal period, the erythema faded, but exfoliation persisted. The parents are healthy but related. One older brother, who died at the age of 3 months, had shown the same clinical picture in the neonatal period and was diagnosed with congenital psoriasis. All clinical investigations, including serum immunoglobulins, complement levels and lymphocyte counts, were normal. Only raised total IgE and multiple positive specific IgE reactions were noted. Skin biopsy revealed an image of ichthyosis. Polarization microscopy of scalp hair showed trichorrhexis nodosa and discrete focal twisting of the hair shaft. This clinical picture and all histological findings are compatible with the indications of Netherton's syndrome. The purpose of this report is to call attention to this severe presentation of congenital ichthyosis in the neonatal period and to the difficulty of a correct diagnosis when confronted with congenital erythroderma.

Erythrokeratodermia variabilis present at birth: case report and review of the literature.

A healthy boy had the distinctive lesions of erythrokeratodermia variabilis (EKV) at birth. Twenty-eight patients described in the literature had EKV that presented in childhood. Nine of the 28 were said to have had a rash since birth, but none were distinctive of EKV. To our knowledge this is the first well-documented case describing a child born with the skin manifestations of EKV. We conclude that patients with EKV are infrequently born with a rash, and that only very rarely when the rash is present is it suggestive of the disorder.

Lethal congenital erythroderma: a newly recognised genetic disorder.

We report 4 patients and their extended families comprising 17 cases, all of whom had congenital exfoliative erythroderma resistant to treatment, associated with failure to thrive and hypoalbuminaemia. All died in the first year of life. This condition appears to be inherited in an autosomal recessive manner and the underlying defect remains unknown.

X-linked dominant Conradi-Hünermann syndrome presenting as congenital erythroderma.

A family with Conradi-Hünermann syndrome was identified after a scaly, erythrodermic neonate was seen. Although examination of the female infant yielded no specific findings suggestive of the syndrome, her mother and maternal great-grandmother had features that allowed the diagnosis to be made. Only after 5 months did the streaky hyperkeratotic pattern characteristic of the syndrome develop in the child. Family members bore other stigmata, including patchy cicatricial alopecia, coarse hair, follicular atrophoderma, frontal bossing, cataracts, short stature, and short proximal limbs. The pattern of inheritance in this family is compatible with that of an X-linked dominant genodermatosis with variable expression. Histopathologic findings from skin biopsy specimens were psoriasiform rather than ichthyotic. Decreased peroxisomal enzyme activity was discovered on fibroblast cultures, linking this syndrome with other peroxisomal disorders. Treatment with oral bezafibrate and clofibrate, which are potential inducers of hepatic peroxisomes, did not result in clinical improvement. It is recommended that usage of the term chondrodysplasia punctata be restricted to the descriptive radiologic finding of stippled calcifications and that Conradi-Hünermann syndrome refer only to the disease described herein, which is transmitted as an X-linked dominant trait.