Once again CGG Repeat Patients, Hypospadia: A Systematic Review
Abstract
High prevalence of hypospadias is only the peak of the iceberg, because there are stigma and isolation, which make not all patients seek a doctor to checkup and do counseling. However, failure of psychical, anatomical and metabolomic development should be faced from the childhood age, adolescent, through the puberty years. One hundred years of congenital adrenal hyperplasia (CAH) in Sweden, open the failure of this labium minor fusion is associated with hypermethylation which have many names. Familial cases, in female, bring this case a gender reversal and reconstructive urology repair, were successful, while the cause, CYP21 mutation/blockade/deficiency also known as cytochrome P450 deficiency is neglected. In prevention, lose with reconstruction, psychologic and environmental which reported due to pesticide are favorite. Digging the cause of labium minus fusion failure, which given the real cause, is need to be chased for prevention in the population.
Method: Systematic review (SR) using Science Direct search engine cross by PubMed, preferable SRand meta-analysis (MA) design than the other.
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Introduction
It is already known that CGG repeat large amount give FMR1 full mutation, while 55-200: permutation associated with psychological and behavior disorder, and FMR1 intermediate, grey zone permutation, and small CGG repeat has also been studied. This epigenetics hypermethylation cases underlie many diseases such as Fragile-X Syndrome, parkinson,1 bipolar,1 autism,1,2 etc. due to silence of DNMT enzyme.3 Hypospadia cause by hormonal disorder, have a Congenital Adrenal Hyperplasia (CAH) disorder (CYP21 deficiency),4 is reported genetics,5 but never epigenetic. Hypospadia could be associated with CGG repeat/ CpG island hypermethylation, -FMR1, -CYP21 mutation. The later is cause by failure of neurosteroid production.6 Hypospadia is a structural marker of FXsyndrome also in CAH, and CAH 100 year in Sweden has been reported.7 The high prevalence of hypospadias is only the tip of an iceberg, because the stigma and exclusion, prevent most sufferers from getting checked by a doctor.8 They avoid seeking medical advice. However, psychological disorder, and fail in anatomical development, as well as metabolism, must be faced by the subjects since childhood, adolescence through puberty.9,10,11,12 Familial, in Congenital Virilizing Adrenal Hyperplasia (CVAH) women the case of gender reversal to male in male rearing are successful managed as male,13 and three reconstructive pediatric urological condition: hypospadia, CAH, and bladder exstrophy have been reported from the perspective of changing expectations and outcomes,14 while the main cause of Cyp21 mutation/blockade/deficiency or cytochrome P450 deficiency is underestimated and become inferior than reconstruction handlers. The psychological and environmental prevention are mentioned due to pesticide in this epigenetics cases.15,16 whereas knockout the enzyme production give hypospadia2 and antenatal androgen excess.17 Exploring the labium minus cause of failure to adhere (hypospadia), the real cause needs to be pursued for mainly prevention purposes. The term CAH covers a number of people of disruptions caused by imperfection in hydroxylation of cortisol precursors. The missing enzyme could be 21-hydroxylase, 17-hydroxylase, 18-hydroxylase, etc. The CYP21 is the mainly steroid missing enzyme gene due to mutation, hypermethylation on CpG islands, blocking, or deficiency. Extremely increasing rate 90% of CAH subjects are made by the alteration of the CYP21 gene on a DNA double helix in 6p21.3.18,19 When a serious autosomal recessive (AR) disorder, which results in influenced homozygotes, has a large occurrence of wide scope population, the account that makes something clear must lie in either avery high mutation rate or in heterozygote advantage. Yupik Eskimos has been reported resistance or advantage in Influenza Bin CAH disorder, an ARgenetic disorder.19 The art icon mask of Yupik Eskimo depicting the bad spirit of the mountain/river, is similar with Escalante syndrome in Argentina (https://commons.wikimedia.org/wiki/File:Mask_depicting_the_Bad_Spirit_of_the_Mountai n,_Yupik_Eskimo,_Yukon_Riv er_area,_probably_St._Michael,_late_1800s,_wood,_paint,_f eathers_-_Dallas_Museum_of_Art_-_DSC04535.jpg). Deficient cortisol production, induce/increased secretion of corticotropin (ACTH). Overproduction of ACTH causing adrenal hyperplasia (CAH). The net effect is a build-up in the adrenal gland of cortisol precursors and androgens.20 The production of more of adrenal androgens is an additional ordinary aspect of it. This hormone amount that is more than necessary results make greater physical size, hairy body, deep voice and double meaning in external genitalia.20 Hypersecretion of adrenal androgens during intrauterine life cause masculinization of the female external genitalia. Increased body growth at an accelerated rate and show advanced skeletal maturation. However, because of premature closing of the epiphyses, their ultimate height is below average.21 Hypospadia 46,XXsuccessfully with reconstruction urology repair,12,13 whereas hypospadia 46,XYreared male or female can lead to successful long-term outcome for the majority of cases.22
Conclusion
Hypermethylation, CGG repeat, CpG island is associated with steroid genes silencing, is the cause of hypospadias, psycho, neuro, metabolism in wet and warm countries high prevalence, which hide by culture, religion and high social stigmatization.
CONFLICT OF INTEREST The author declares nothing.
