China
Africa
Explore chapters and articles related to this topic
Endocrine and reproductive disorders
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
The complexities of this group have become greatly clarified with isolation of specific genes on the Y and X chromosomes involved with sex determination. A careful endocrine, cytogenetic and molecular assessment is essential before genetic counselling can be given. The main disorders include XX males and XY females: XX males: These are usually sporadic, resulting from Y chromosome material including the SRY gene translocated onto an X chromosome and usually detectable by molecular tests.XY females: The most frequent cause is the androgen insensitivity syndrome (formerly known as testicular feminisation) where a normal female phenotype is associated with the presence of testes. This diagnosis may not be suspected until failure of menarche or absent pubic and axillary hair is investigated. Partial androgen insensitivity may result in ambiguous genitalia at birth. In XY gonadal dysgenesis, due to molecular defects in the Y-linked sex-determining SRY gene, or to corresponding X-linked defects, there may be a normal phenotype or varying degrees of intersex. The dysgenetic gonad is at risk of malignant change and should be removed. Both these disorders may follow X-linked recessive inheritance with phenotypic and chromosomally normal female relatives at risk of having an affected XY daughter.Ambiguous genitalia: This may result from some of the conditions mentioned previously (e.g. CAH, sex chromosome disorders), from partial androgen insensitivity, from disorders involving the SRY, SOX9 or WT1 genes, associated with campomelic dysplasia, Wilms tumour, the Denys-Drash syndrome and other genital anomalies). It will require careful endocrine, chromosome and clinical assessment to be sure of the cause.
Chylous Ascites in an Infant with Thanatophoric Dysplasia Type I with FGFR3 Mutation Surviving Five Months
Published in Fetal and Pediatric Pathology, 2018
Jeon Soo-kyeong, Narae Lee, Mi Hye Bae, Young Mi Han, Kyung Hee Park, Shin Yun Byun
Since there is no curative treatment available for TD, if prenatal ultrasonographic findings are almost definitive, termination of pregnancy based on consultation with the parent is usually the preferred treatment option. Early prenatal diagnosis of TD is possible based upon observation of the characteristic findings on ultrasonography performed during the second trimester of pregnancy. However, it might be difficult to distinguish the condition from other types of skeletal dysplasia, such as achondrogenesis, dyssegmental dysplasia, Silverman-Handmaker type, campomelic dysplasia, and rhizomelic chondrodysplasia punctate, based on ultrasonography alone. In such cases, molecular genetic analysis of the FGFR3 gene may be useful for prenatal diagnosis. Sawai et al. were the first to report on the prenatal diagnosis of TD by mutational analysis of the gene using amniocentesis (25). Prenatal diagnosis makes it possible to opt for elective abortion, which can help avoid subsequent difficulties, for example, difficult vaginal delivery due to hydrocephalus and cesarean section (10).
Molecular diagnostics of disorders of sexual development: an Indian survey and systems biology perspective
Published in Systems Biology in Reproductive Medicine, 2019
MR Nagaraja, Satya Prakash Gubbala, C. R. Wilma Delphine Silvia, Ramars Amanchy
SOX9 mutations have been implicated in campomelic dysplasia with autosomal sex reversal (OMIM 114290), associated with CTNNB1 (encodes for catenin beta 1 protein, mutations cause ovarian cancer), that plays a key role in genetic regulation of testis and ovary development (Eggers et al. 2014). Similarly its associations with PRKACA (encodes cAMP-dependent protein kinase catalytic subunit α) implicated in Cushing’s syndrome have proven associations with oocyte maturation (Yoon et al. 2018). Also, PRKACG (encodes for cAMP-dependent protein kinase catalytic subunit γ) mutation has been identified as a candidate gene for 46,XY gonadal dysgenesis (Norling et al. 2013).
Prenatal diagnosis of campomelic dysplasia due to SOX9 deletion
Published in Journal of Obstetrics and Gynaecology, 2019
Gulsum Kayhan, Pınar Calis, Deniz Karcaaltincaba, Esra Tug
Campomelic dysplasia (CD, OMIM #114290) is an autosomal dominant and severe skeletal dysplasia which is characterised by the congenital shortness and bowing of the long bones (i.e., campomelia), hypoplastic scapulae, deformed pelvis and spine, 11 pairs of ribs, Robin sequence, laringomalasia, and the sexual differentiation disorder from ambiguous genitalia to complete 46, XY sex reversal (Maroteaux et al. 1971). Other findings of CD include a relative macrocephaly, flat face, and the dislocation of the hips, scoliosis, club feet, hearing loss, and, more rarely, and heart anomalies. Most patients die in the neonatal period due to respiratory distress (Matsushita et al. 2013).