RESUMO
We present a case of iatrogenic Cushing syndrome and adrenal insufficiency in a newborn secondary to an overuse of triamcinolone cream 0.1% prescrived for the treatment of diaper dermatitis.This case highlignts the risks of systemic absorption when prescribing topical medications in the diaper area of an infant, and the importance of caution and proper follow up when prescribing even mid potency steroids to pediatric patients. .
Assuntos
Síndrome de Cushing , Dermatite das Fraldas , Administração Tópica , Síndrome de Cushing/induzido quimicamente , Dermatite das Fraldas/tratamento farmacológico , Glucocorticoides/efeitos adversos , Humanos , Lactente , Recém-Nascido , Triancinolona/efeitos adversosRESUMO
The NR5A1 gene encodes for steroidogenic factor 1, a nuclear receptor that regulates proper adrenal and gonadal development and function. Mutations identified by NR5A1 sequencing have been associated with disorders of sex development (DSD), ranging from sex reversal to severe hypospadias in 46,XY patients and premature ovarian failure (POF) in 46,XX patients. Previous reports have identified four families with a history of both 46,XY DSD and 46,XX POF carrying segregating NR5A1 sequence mutations. Recently, three 46,XY DSD sporadic cases with NR5A1 microdeletions have been reported. Here, we identify the first NR5A1 microdeletion transmitted in a pedigree with both 46,XY DSD and 46,XX POF. A 46,XY individual with DSD due to gonadal dysgenesis was born to a young mother who developed POF. Array CGH analysis revealed a maternally inherited 0.23 Mb microdeletion of chromosome 9q33.3, including the NR5A1 gene. Based on this finding, we screened patients with unexplained 46,XY DSD (n = 11), proximal hypospadias (n = 21) and 46,XX POF (n = 36) for possible NR5A1 copy-number variations (CNVs) via multiplex ligation-dependent probe amplification (MLPA), but did not identify any additional CNVs involving NR5A1. These data suggest that NR5A1 CNVs are an infrequent cause of these disorders but that array CGH and MLPA are useful genomic screening tools to uncover the genetic basis of such unexplained cases. This case is the first report of a familial NR5A1 CNV transmitting in a pedigree, causing both the male and female phenotypes associated with NR5A1 mutations, and the first report of a NR5A1 CNV associated with POF.
Assuntos
Variações do Número de Cópias de DNA , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Transtorno 46,XY do Desenvolvimento Sexual/genética , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/genética , Fator Esteroidogênico 1/genética , Adulto , Sequência de Bases , Pontos de Quebra do Cromossomo , Deleção Cromossômica , Cromossomos Humanos Par 9 , Feminino , Humanos , Recém-Nascido , Masculino , Dados de Sequência Molecular , Mutação , Linhagem , FenótipoRESUMO
CONTEXT: A rare presentation of hypothalamic tumors in infants and young children is profound emaciation and generalized loss of sc adipose tissue, also known as "diencephalic syndrome." Similar loss of sc fat can be observed in children with acquired generalized lipodystrophy or congenital generalized lipodystrophy. Precise diagnosis may be challenging early in the course of the disease, especially in the absence of metabolic abnormalities. CASE DESCRIPTION: We report three males who presented with poor weight gain and generalized loss of sc fat at birth to 3 years of age consistent with generalized lipodystrophy, with subsequent development of pilocytic astrocytoma. Two of them had hypothalamic tumors, and one had a multicentric tumor with a large right parietal mass. Our patients are unique because the onset of lipodystrophy occurred 2.5 to 7.3 years before the diagnosis of brain tumor, and all of them gained body fat or weight after surgical removal and/or chemotherapy. One patient had hepatosplenomegaly and impaired glucose tolerance, and another patient had severe hyperglycemia and hypertriglyceridemia during the course of the disease. Two patients presented with central precocious puberty and advanced bone age at the chronological age of 6 years. CONCLUSIONS: It is likely that pilocytic astrocytoma may induce generalized lipodystrophy by paraneoplastic antiadipocyte antibody formation or by excessive hormones or cytokine secretion resulting in excess lipolysis from adipocytes. We conclude that young children presenting with idiopathic acquired generalized lipodystrophy or atypical congenital generalized lipodystrophy, with or without metabolic abnormalities, should prompt investigation for brain tumors.