RESUMO
There are multiple etiologies for fetal dilated bowel loops on ultrasonography (US), and we present a unique case of male siblings with a forkhead box P3 (FOXP3) mutation. Both children presented with fetal bowel anomalies on prenatal US. Family histories of cystic fibrosis and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome were reported. Amniocentesis in both pregnancies identified a normal male karyotype and the familial mutation associated with IPEX syndrome. IPEX syndrome is one of a group of conditions known as congenital diarrhea disorders. Other congenital diarrhea disorder cases have presented with similar prenatal US findings. As a result of these associations, we suggest considering IPEX syndrome as a potential cause of fetal bowel anomalies, particularly with a known family history. However, continued research into the phenotypic and genotypic correlations for IPEX syndrome is likely needed to better understand this possible prenatal presentation.
Assuntos
Diabetes Mellitus Tipo 1/congênito , Diarreia/diagnóstico por imagem , Diarreia/genética , Fatores de Transcrição Forkhead/genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico por imagem , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças do Sistema Imunitário/congênito , Mutação/genética , Ultrassonografia Pré-Natal/métodos , Adulto , Transplante de Medula Óssea , Diabetes Mellitus Tipo 1/diagnóstico por imagem , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/terapia , Diarreia/terapia , Evolução Fatal , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Doenças do Sistema Imunitário/diagnóstico por imagem , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/terapia , Lactente , Recém-Nascido , Intestinos/diagnóstico por imagem , Masculino , Gravidez , IrmãosRESUMO
Congenital diarrheal disorders (CDDs) are early-onset enteropathies generally inherited as autosomal recessive traits. Most patients with CDDs require rapid diagnosis as they need immediate and specific therapy to avoid a poor prognosis, but their clinical picture is often overlapping with a myriad of nongenetic diarrheal diseases. We developed a next-generation sequencing (NGS) panel for the analysis of 92 CDD-related genes, by which we analyzed patients suspect for CDD, among which were (i) three patients with sucrose-isomaltase deficiency; (ii) four patients with microvillous inclusion disease; (iii) five patients with congenital tufting enteropathy; (iv) eight patients with glucose-galactose malabsorption; (v) five patients with congenital chloride diarrhea. In all cases, we identified the mutations in the disease-gene, among which were several novel mutations for which we defined pathogenicity using a combination of bioinformatic tools. Although CDDs are rare, all together, they have an incidence of about 1%. Considering that the clinical picture of these disorders is often confusing, a CDD-related multigene NGS panel contributes to unequivocal and rapid diagnosis, which also reduces the need for invasive procedures.