ABSTRACT
Schinzel-Giedion syndrome is a rare autosomal dominant disorder comprising postnatal growth failure, profound developmental delay, seizures, facial dysmorphisms, genitourinary, skeletal, neurological, and cardiac defects. It was recently revealed that Schinzel-Giedion syndrome is caused by de novo mutations in SETBP1, but there are few reports of this syndrome with molecular confirmation. We describe two unrelated Brazilian patients with Schinzel-Giedion syndrome, one of them carrying a novel mutation. We also present a review of clinical manifestations of the syndrome, comparing our cases to patients reported in literature emphasizing the importance of the facial gestalt associated with neurological involvement for diagnostic suspicion of this syndrome.
Subject(s)
Abnormalities, Multiple/genetics , Carrier Proteins/genetics , Craniofacial Abnormalities/genetics , Face/physiopathology , Hand Deformities, Congenital/genetics , Intellectual Disability/genetics , Nails, Malformed/genetics , Nuclear Proteins/genetics , Abnormalities, Multiple/physiopathology , Brazil , Child , Craniofacial Abnormalities/physiopathology , Female , Hand Deformities, Congenital/physiopathology , Humans , Hydronephrosis/genetics , Hydronephrosis/physiopathology , Infant , Intellectual Disability/physiopathology , Male , Mutation , Nails, Malformed/physiopathology , Seizures/genetics , Seizures/physiopathology , Sequence Analysis, DNAABSTRACT
AIM: The angiotensin type 2 (AT2 ) receptor takes part in the process of ureteric bud during kidney development. Therefore, the gene encoding AT2 receptor, the AGTR2 gene located in the X chromosome, is a potential candidate for genetic association with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). This study aimed to investigate whether AGTR2 gene polymorphisms are associated with CAKUT in general or even with common phenotypes of CAKUT in a Brazilian sample of paediatric patients. METHODS: We analyzed 290 paediatric patients with CAKUT and 262 healthy controls from the same geographic area. TaqMan single-nucleotide polymorphism (SNP) genotyping assays for AGTR2 gene at rs1403543, rs3736556, rs35474657, rs5193 and rs5194 were performed. The sample was in Hardy-Weinberg Equilibrium for all five SNPs. RESULTS: The presence of CAKUT in general was not significantly associated with the SNPs included in this study. However, when patients were segregated according to major phenotypes, the diagnosis of Ureteropelvic Junction Obstruction (UPJO) was significantly associated with AGTR2 gene polymorphisms at rs3736556 and at rs5194. On the other hand, the diagnoses of vesicoureteral reflux and of multicystic dysplastic kidney were not associated with AGTR2 gene polymorphisms. CONCLUSION: Our results support that the AGTR2 gene may contribute to the pathogenesis of UPJO and the genetic origin of CAKUT could vary according to phenotype expression.
Subject(s)
Hydronephrosis/congenital , Multicystic Dysplastic Kidney/genetics , Polymorphism, Single Nucleotide , Receptor, Angiotensin, Type 2/genetics , Ureteral Obstruction/genetics , Brazil , Child , Child, Preschool , Female , Humans , Hydronephrosis/genetics , Male , PhenotypeABSTRACT
Schinzel-Giedion syndrome is a rare autosomal recessive disorder characterized by coarse facies, midface retraction, hypertrichosis, multiple skeletal anomalies, and cardiac and renal malformations. Craniofacial abnormalities of this syndrome sometimes resemble a storage or metabolic disease. The pathogenesis of the disease remains unknown. The objective of this report was to emphasize the importance of congenital bilateral hydronephrosis for the diagnosis of Schinzel-Giedion syndrome. We describe the first Brazilian case of a newborn with typical facies, generalized hypertrichosis, cardiac and skeletal anomalies, and bilateral hydronephrosis detected during pregnancy and confirmed later by abdominal ultrasonography. Chromosomal constitution was normal. Of the 35 cases already reported in the literature, 31 presented hydronephrosis, which is considered an important clue in diagnosis. If Schinzel-Giedion syndrome were indexed as a cause of congenital hydronephrosis, its identification would be greatly facilitated, since the majority of the other findings in Schinzel-Giedion syndrome are nonspecific and common to many genetic syndromes.
Subject(s)
Abnormalities, Multiple/diagnosis , Hydronephrosis/congenital , Abnormalities, Multiple/genetics , Face/abnormalities , Facies , Fatal Outcome , Female , Humans , Hydronephrosis/genetics , Infant, Newborn , Kidney/abnormalities , SyndromeABSTRACT
A síndrome de Schinzel-Giedion é uma patologia genética rara de etiologia desconhecida e herança autossômica recessiva. Caracteriza-se pela presença de um fácies grotesco, hipoplasia da porção média da face, hipertricose, múltiplas anomalias esqueléticas, malformações cardíacas e renais.As anomalias craniofaciais desta síndrome podem lembrar o fácies de uma doença metabólica de depósito. O objetivo deste relato foi enfatizar a importância da hidronefrose congênita bilateral no diagnóstico da síndrome de Schinzel-Giedion . Descrevemos o primeiro caso brasileiro de um recém-nascido com fácies típico, hipertricose generalizada, anomalias esqueléticas, cardíacas e hidronefrose bilateral, detectada pela ultrassonografia fetal e, posteriormente, confirmada pelo mesmo método. O estudo cromosômico foi normal. Na literatura, de 35 casos descritos, 31 apresentavam hidronefrose, o que constitui um achado fundamental para o diagnóstico da patologia. Dessa forma, acreditamos que se a síndrome de Schinzel-Giedion fosse indexada como uma das causas de hidronefrose congênita, seu diagnóstico seria facilitado, uma vez que a maioria dos outros achados desta síndrome, com exceção da hidronefrose, é inespecífica e comum a diversas outras síndromes genéticas.