Acantholytic ectodermal dysplasia: clinicopathological study of a new desmosomal disorder.

We describe two boys with curly hair, palmoplantar keratoderma and skin fragility who presented clinical and histological features similar, but not identical, to those exhibited by patients with ectodermal dysplasia-skin fragility syndrome (McGrath syndrome) and other genetic desmosomal defects such as Carvajal syndrome and Naxos disease. Clinical features included trauma-induced blisters and erosions, palmoplantar keratoderma and hyperkeratotic, fissured plaques with perioral involvement. The patients had abundant curly scalp hair, and normal eyebrows and eyelashes. Sweating was normal. Nails were normal at birth but subsequently showed secondary dystrophy. Histopathological analysis of the skin demonstrated acantholysis and intercellular widening of the spinous and granular layers in involved regions. No involvement of scalp skin was seen. Desmosomes were markedly reduced in number and poorly developed with no clear insertions of the keratin filaments. The latter were clumped around the nuclei. Immunostaining of patient skin with antibodies raised against key desmosomal proteins demonstrated disrupted expression of desmoplakin, plakoglobin and desmoglein 1. Additional studies of the family history and of the desmoplakin, plakoglobin and desmoglein 1 genotype for both patients may help further elucidate the molecular cause of this variation on ectodermal dysplasia-skin fragility syndrome.

[Linear Darier disease in two siblings. An example of loss of heterozygosity]. / Maladie de Darier linéaire dans une fratrie. Un exemple de perte d'hétérogénéité.

BACKGROUND: Darier's disease or keratosis follicularis is an autosomal dominant acantholytic disorder that frequently arises as a result of spontaneous mutation. It is either a generalized or localized condition due to a mutation in the SERCA2 12q23-q24,1 resulting in a faulty organization of the tonofilaments. We present two siblings affected with the linear form of this disorder and discuss these cases as an example of the genetic mechanism of loss of heterozygosity. CASE REPORTS: A 7 year-old girl was referred for evaluation of linear lesions present since the first year of age. Examination disclosed red, 1 to 2 mm papules that coalesced to form linear plaques on the left side of the vulvar and perianal areas, and on the left hand and foot. Her older brother had similar lesions in a linear arrangement on the left side of the face neck and homolateral foot. No lesions were found in their parents. Biopsies of both affected children revealed an intraepidermal suprabasal cleft. Dyskeratotic cells were present in the spinous layer, and corps ronds and grains near the granular layer. DISCUSSION: The linear form of Darier's disease could result from genetic mosaicism for this autosomal dominant disorder. As these children have a more pronounced involvement than the usual Darier's disease lesions, disposed in a linear arrangement, they probably represent a type 2 segmental manifestation of the disorder. Likewise, the presence of the same linear disorder in two siblings could be explained by loss of heterozygosity for the Darier's disease gene.

Costello syndrome: report of a new case with choanal atresia and fatal outcome.

We describe a girl with motor and mental retardation, macrocephaly, a "coarse" face, choanal atresia, postnatal feeding difficulty, redundant skin with deep palmar and plantar creases, and histopathological evidence of altered elastic fibers, who died at the age of 11 months. We believe this represents another case of Costello syndrome. Lacking papillomata, she had choanal atresia and underwent a fatal outcome at an early age. The differential diagnosis of cutis laxa in association with postnatal growth retardation and developmental delay and with cardio-facio-cutaneous and Noonan syndromes is discussed.

Cerebriform plantar hyperplasia: ultrastructural study of two cases.

In the present work we report the histopathological features of the cerebriform plantar hyperplasia observed in two patients with a mild form of the Proteus syndrome. Light microscopy revealed increased fibro-adipose tissue and adnexal structures in the dermis. Ultrastructurally, densely packed collagen fibrils variable in diameter and configuration, described as composite fibrils and unraveled fibrils, as well as a few fragmented elastic fibrils presenting an altered ratio between the elastin and the microfibrillar components were the major features observed. We consider that these histopathological findings will contribute to further delineate cerebriform plantar hyperplasia and also to establish clues for the early diagnosis of the Proteus syndrome.

Phacomatosis pigmentokeratotica: another epidermal nevus syndrome and a distinctive type of twin spotting.

The name epidermal nevus syndrome could be applied to a group of clinically and histopathologically different entities as has been pointed out by Happle. Phacomatosis pigmentokeratotica is a further type of epidermal nevus syndrome distinguished by the presence of a sebaceous nevus and a contralateral speckled lentiginous nevus of the papular type, associated with skeletal or neurological abnormalities. Three new cases of this recently delineated syndrome are presented. A common origin may account for the temporal and spatial relationship between the epidermal and the speckled lentiginous nevus. The concept of melanocytic-epidermal twin spotting similar to the interpretation of vascular twin spotting could explain the pathogenesis of this entity.

Atrichia, ichthyosis, follicular hyperkeratosis, chronic candidiasis, keratitis, seizures, mental retardation and inguinal hernia: a severe manifestation of IFAP syndrome?

A boy with congenital atrichia, ichthyosis follicular, keratitis, cutaneous infections and a huge inguinal hernia, but without deafness is reported. We believe it represents a new case of a rare X-linked recessive syndrome known as ichthyosis follicularis, alopecia, photophobia syndrome (IFAP). The differential diagnosis from keratitis ichthyosis deafness is discussed. The cutaneous infections seen in our case suggest the possibility of considering a genetic link between these syndromes.

Blue rubber bleb nevus (Bean syndrome): evolution of four cases and clinical response to pharmacologic agents.

Blue rubber bleb nevus (BRBN) syndrome is a rare disorder characterized by distinctive cutaneous and gastrointestinal vascular malformations. The latter may lead to bleeding complications. We followed four affected children for at least 5 years. The evolution of their disease and the value of pharmacologic agents (steroids, interferon) in the management of some of these patients are discussed.

Wrinkly skin syndrome: ultrastructural alterations of the elastic fibers.

We report the clinical and pathologic features of a patient with wrinkly skin syndrome. The essential clinical features were wrinkly skin with poor elasticity over the abdomen and on the dorsum of the hands and feet, increased palmar and plantar creases, and a prominent venous pattern over the chest. On light microscopy, histopathologic findings included appreciable heterogeneity in the structure, amount, and distribution pattern of elastic fibers. Agglutination and fragmentation of the microfibrillar component and a remarkable decrease in elastin were the major ultrastructural features. The differential diagnosis with other connective tissue disorders is discussed.

Displasia oculodentodigital e hipomelanosisde ito: a proposito de un caso / Oculodentadigital displasia and hypomelanosis of ito: in conection with a case

El caso aqui presentado manifiesta anomalias descriptas en la I.P.A.y en la D.O.D.D. Si bien la I.P.A.puede asociarse con la mayoria de los defectos descriptos en el paciente,la facies caracteristica, el acortamiento del quinto dedo de manos y pies, el defecto del esmalte dentario y la presencia de similares alteraciones en el padre, sin presentar antecedentes de maculas hipocromicas ni de los otros defectos asociados que se hallan en el nini, nos hacen pensar que se trata de la asociacion fortuita de dos sindromes neurocutaneos

Displasia oculodentodigital e hipomelanosisde ito: a proposito de un caso / Oculodentadigital displasia and hypomelanosis of ito: in conection with a case

El caso aqui presentado manifiesta anomalias descriptas en la I.P.A.y en la D.O.D.D. Si bien la I.P.A.puede asociarse con la mayoria de los defectos descriptos en el paciente,la facies caracteristica, el acortamiento del quinto dedo de manos y pies, el defecto del esmalte dentario y la presencia de similares alteraciones en el padre, sin presentar antecedentes de maculas hipocromicas ni de los otros defectos asociados que se hallan en el nini, nos hacen pensar que se trata de la asociacion fortuita de dos sindromes neurocutaneos