1/124. Bilateral wilms tumor in a boy with severe hypospadias and cryptochidism due to a heterozygous mutation in the WT1 gene.Mutations in the WT1 gene causing Wilms tumors were first reported in wagr syndrome (wilms tumor, aniridia, Genitourinary malformation, mental Retardation) and Denys Drash syndrome (pseudohermaphroditism, wilms tumor, nephropathy), but only in a few patients with hypospadias and cryptorchidism without other signs of Denys Drash (DDS) or wagr syndrome WT1 mutations were identified. We report a boy, who was born in 1989 with hypospadias and bilateral cryptorchidism. Previous karyotyping and endocrine studies had ruled out any known cause of male pseudohermaphroditism. Subsequently, he developed a bilateral wilms tumor, which was detected by palpation at the age of 15 months during a routine visit by the general pediatrician. Because of its extensive size, surgery and chemotherapy were needed for treatment. Analysis of the WT1 gene was performed 5 y after diagnosis and revealed a C to T transition in one allele generating a stop codon at codon 362 and subsequently leading to a truncated protein with loss of its ability to bind to dna. No signs of DDS or wagr syndrome are present in the boy. The work up of this patient and the so far known few comparable cases from the literature lead to the conclusion that in newborns with severe urogenital malformations not due to known chromosomal or endocrine disorders mutational screening of the WT1 gene should be performed, to evaluate the high risk of developing a wilms tumor. We favor mutational screening in these patients as an easy tool for investigation, because in the future it will probably decrease the necessity of frequent control visits in patients without a WT1 mutation.- - - - - - - - - - ranking = 1keywords = gene (Clic here for more details about this article) |
2/124. Homozygous alpha-thalassaemia and hypospadias--common aetiology or incidental association? Long-term survival of Hb Bart's hydrops syndrome leads to new aspects for counselling of alpha-thalassaemic traits.Fetuses with homozygous alpha-thalassaemia develop Hb Bart's hydrops fetalis syndrome, which usually leads either to abortion or fetal/neonatal death. We report diagnosis, intrauterine transfusion therapy, neonatal intensive care management and long-term follow-up of a Vietnamese infant who survived Hb Bart's hydrops fetalis syndrome. During the first 2 years the child had normal development. In addition, the patient exhibited penoscrotal hypospadias. Despite a thorough endocrinological work-up the aetiology of genital ambiguity could not be elucidated. A review of the literature showed an association of homozygous alpha-thalassaemia and hypospadias in all surviving male children, suggesting a common aetiology for both entities. CONCLUSION: On the basis of our findings, we speculate that an unknown gene on chromosome 16 responsible for genital formation is altered in homozygous alpha-thalassaemia.- - - - - - - - - - ranking = 0.11111111111111keywords = gene (Clic here for more details about this article) |
3/124. Homozygous alpha-thalassemia associated with hypospadias in three survivors.We report three cases of homozygous alpha-thalassemia (alphaTH) who survived beyond the neonatal period, all with hypospadias. A review of literature identified two additional male cases of homozygous alphaTH who survived, and both had hypospadias. The simultaneous occurrence of the two conditions seems beyond coincidence and may be causally related. Possible pathogenesis for the association may be 1) homozygous alphaTH-induced in utero and/or edema secondary to hydrops fetalis, both leading to the failure of proper fusion of the urogenital folds, or 2) defect of another gene located at a chromosome 16p13.3 region. Thus, parents who request intrauterine therapy for a male fetus with homozygous alphaTH should be informed about this association and its prognosis.- - - - - - - - - - ranking = 0.22222222222222keywords = gene (Clic here for more details about this article) |
4/124. Three cases of congenital growth hormone deficiency with micropenis and hypospadias: what does growth hormone have to do with it?This paper reports 3 cases of congenital GH deficiency with male pseudohermaphroditism. All 3 showed a normal male karyotype, hypospadias of different degrees, and, for 2 of them, micropenis. No mullerian structure was individualized since pelvic ultrasound and genitography were normal. Patient 1 was born with multiple anomalies and patient 3 showed partial agenesia of the corpus callosum. Only 1 patient showed complete anterior pituitary deficiency. Gonadotropin defects were not investigated. We postulate that GH might play a role in early testosterone stimulation, and thus in male sexual differentiation.- - - - - - - - - - ranking = 0.11111111111111keywords = gene (Clic here for more details about this article) |
5/124. The novel contiguous gene syndrome of myotubular myopathy (MTM1), male hypogenitalism and deletion in Xq28:report of the first familial case.Hu et al. (1996) and Laporte et al. (1997) recently proposed a novel contiguous gene syndrome of myotubular myopathy, abnormal male genital development and deletion in Xq28. We studied a family where two male infants, both deceased, had myotubular myopathy and intersexual genitalia. Using FISH we detected in the mother a hemizygous deletion including the myotubularin gene MTM1 and F18 (a gene of yet unknown function). dna studies with STR-markers (short tandem repeats) within and flanking the deleted segment confirmed the deletion in the family and were used for prenatal diagnosis. Our findings confirm the existence of this novel contiguous gene syndrome and support that the deletion of the F18 gene, or a neighboring gene, may cause ambiguous genitalia or severe hypospadias in males. The mother had low muscle power and marked menstrual irregularities which may indicate that she is a manifesting carrier and that the deletion may include a gene (F18 or other) for gonadal function in females.- - - - - - - - - - ranking = 1.2222222222222keywords = gene (Clic here for more details about this article) |
6/124. New frameshift mutation in the 5alpha-reductase type 2 gene in a Brazilian patient with 5alpha-reductase deficiency.Male pseudohermaphroditism caused by steroid 5alpha-reductase deficiency is an autosomal recessive disorder. The enzyme steroid 5alpha-reductase 2 (encoded by the SRD5A2 gene) catalyses the conversion of testosterone to dihydrotestosterone, which is required for normal differentiation of the external male genitalia. This report describes the molecular analysis of the 5alpha-reductase type 2 gene in a Brazilian patient who was raised as a female, underwent a reversal of gender role behavior, and is now a married man. This patient is a compound heterozygote bearing an A-->G mutation within exon 2, changing codon 126 from Glu to Arg on one allele and a novel single base deletion (418delT) causing a frameshift mutation at codon 140 in the same exon, on the other allele. This last mutation probably leads to the synthesis of a truncated protein, because a premature termination signal is created at codon 159.- - - - - - - - - - ranking = 0.66666666666667keywords = gene (Clic here for more details about this article) |
7/124. Prenatal karyotype and ultrasound discordance in intersex conditions.An infant born at 38 weeks' gestation with ambiguous genitalia had a prenatal 45X karyotype but an enlarged phallus on an ultrasound scan at 31 weeks' gestation. The newborn examination demonstrated penoscrotal hypospadias with chordee and two gonads palpable in the scrotum with a right hydrocele. Ultrasound showed a saccular structure containing debris behind the bladder. The postnatal karyotype was revealed to be 45X/46XY, with a pseudodicentric y chromosome. cystoscopy/genitography identified a uterus and a right fallopian tube, which were removed along with a dysgenetic right gonad. biopsy of the descended left gonad revealed rare germ cells. The final diagnosis was 45X/46XY male pseudohermaphroditism with testicular dysgenesis. One should be aware of possible chromosomal mosaicism and combine the prenatal karyotype with the ultrasound genital findings to formulate an intersex differential diagnosis.- - - - - - - - - - ranking = 0.22222222222222keywords = gene (Clic here for more details about this article) |
8/124. Penoscrotal hypospadias and coarctation of the aorta with mixed gonadal dysgenesis.A 45,X/46,Xidic(Y)(q11.2) mosaicism was found in a 4-year-old boy. The clinical appearance was characterized by bilateral cryptorchidism, penoscrotal hypospadias, short penis, and coarctation of the aorta. The latter is the only abnormality also seen in turner syndrome. A biopsy of the gonads revealed normal prepubertal testicular tissue. A chromosome analysis in all boys with penoscrotal, scrotal, or perineal hypospadias and a thorough examination of the heart in children with 45,X/46,XY mosaicism are recommended.- - - - - - - - - - ranking = 0.44444444444444keywords = gene (Clic here for more details about this article) |
9/124. Congenital urethrocutaneous fistula.Congenital urethral fistula is an extremely rare but easily manageable anomaly that may be confused with hypospadias. This is a case description of a congenital fistula of the anterior urethra. awareness of the entity will avoid complications.- - - - - - - - - - ranking = 1.2442793124078keywords = anomaly (Clic here for more details about this article) |
10/124. Penoscrotal inversion, hypospadias, imperforate anus, facial anomalies, and developmental delay: definition of a new clinical syndrome.We describe a 2-month-old boy with penoscrotal inversion, hypospadias, imperforate anus, facial anomalies, developmental retardation, and a subtelomeric deletion of chromosome 13q. His phenotype with anogenital malformations and characteristic facies closely resembled two unrelated patients with minute deletions of chromosome 13q who we reported earlier. In addition, he had unilateral renal agenesis. We propose that these patients represent a clinically recognizable, novel chromosomal microdeletion syndrome. The findings indicate the presence of a major gene(s) on chromosome 13q33.2qter that regulate(s) the migration and development of ano-reno-genital cells and organs. We speculate that mutations of this developmental gene(s) may also result in more frequent congenital malformations (isolated hypospadias, uterus bicornis, unilateral renal agenesis). Additional studies are needed to further delineate the genetic defect.- - - - - - - - - - ranking = 1.9852110992441keywords = mental retardation, gene (Clic here for more details about this article) |
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