scholarly journals Parent-Rated Severity of Illness and Anxiety among Caregivers of Children Born with a Disorder of Sex Development Including Ambiguous Genitalia

2018 ◽  
Vol 90 (5) ◽  
pp. 308-313 ◽  
Author(s):  
Christina M. Sharkey ◽  
Dana M. Bakula ◽  
Cortney Wolfe-Christensen ◽  
Paul Austin ◽  
Laurence Baskin ◽  
...  
Keyword(s):  
Strong Predictor ◽  
Disorders Of Sex Development ◽  
Severity Of Illness ◽  
Ambiguous Genitalia ◽  
Parental Anxiety ◽  
Hydroxylase Deficiency ◽  
Sex Development ◽  
Time Interaction ◽  
21 Hydroxylase Deficiency ◽  
Over Time

Background/Aims: Parents of children born with disorders of sex development (DSD) often experience anxiety, but risk factors, including parental perception of the severity of their child’s DSD, have not been examined. We hypothesized that severity of illness (SOI) ratings would relate to parental anxiety, and would be higher for parents of children with a potentially life-threatening DSD (e.g., 21-hydroxylase deficiency). Methods: Eighty-nine parents (Mage = 33.0, 56.2% mothers) of 51 children (Mage in months = 8.7) with a DSD including ambiguous genitalia were recruited from 12 specialized DSD clinics. Parents completed questionnaires prior to genitoplasty, 6 months post-genitoplasty, and 12 months post-genitoplasty (if completed). Data were analyzed with linear mixed modeling. Results: Parental anxiety decreased over time, χ2(1) = 10.14, p < 0.01. A positive relationship between SOI and anxiety was found, with SOI being a strong predictor of anxiety (b = 0.53, p < 0.01; χ2[1] = 5.33, p < 0.05). An SOI by time interaction indicated SOI had an increasing effect on anxiety over time, b = 0.06, p < 0.05; χ2(1) = 6.30, p < 0.05. There was no diagnosis by SOI interaction. Conclusion: Parental anxiety decreased over time, but those with higher SOI ratings reported greater initial anxiety followed by slower resolution over time. Underlying etiology of DSD had no effect on the relationship between SOI and anxiety.

scholarly journals 408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Georgette Beatriz De Paula ◽  
Beatriz Amstalden Barros ◽  
Stela Carpini ◽  
Bruna Jordan Tincani ◽  
Tais Nitsch Mazzola ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Gonadal Dysgenesis ◽  
Disorders Of Sex Development ◽  
Ambiguous Genitalia ◽  
Gonadal Development ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Genital Ambiguity ◽  
21 Hydroxylase Deficiency

Objective. To evaluate diagnosis, age of referral, karyotype, and sex of rearing of cases with disorders of sex development (DSD) with ambiguous genitalia.Methods. Retrospective study during 23 years at outpatient clinic of a referral center.Results. There were 408 cases; 250 (61.3%) were 46,XY and 124 (30.4%) 46,XX and 34 (8.3%) had sex chromosomes abnormalities. 189 (46.3%) had 46,XY testicular DSD, 105 (25.7%) 46,XX ovarian DSD, 95 (23.3%) disorders of gonadal development (DGD), and 19 (4.7%) complex malformations. The main etiology of 46,XX ovarian DSD was salt-wasting 21-hydroxylase deficiency. In 46,XX and 46,XY groups, other malformations were observed. In the DGD group, 46,XY partial gonadal dysgenesis, mixed gonadal dysgenesis, and ovotesticular DSD were more frequent. Low birth weight was observed in 42 cases of idiopathic 46,XY testicular DSD. The average age at diagnosis was 31.7 months. The final sex of rearing was male in 238 cases and female in 170. Only 6.6% (27 cases) needed sex reassignment.Conclusions. In this large DSD sample with ambiguous genitalia, the 46,XY karyotype was the most frequent; in turn, congenital adrenal hyperplasia was the most frequent etiology. Malformations associated with DSD were common in all groups and low birth weight was associated with idiopathic 46,XY testicular DSD.

scholarly journals Disorders of Sex Development of Adrenal Origin

2021 ◽  
Vol 12 ◽  
Author(s):  
Gabriela P. Finkielstain ◽  
Ana Vieites ◽  
Ignacio Bergadá ◽  
Rodolfo A. Rey
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Special Focus ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Trophic Effect ◽  
Salt Wasting ◽  
Sex Development ◽  
21 Hydroxylase Deficiency

Disorders of Sex Development (DSD) are anomalies occurring in the process of fetal sexual differentiation that result in a discordance between the chromosomal sex and the sex of the gonads and/or the internal and/or external genitalia. Congenital disorders affecting adrenal function may be associated with DSD in both 46,XX and 46,XY individuals, but the pathogenic mechanisms differ. While in 46,XX cases, the adrenal steroidogenic disorder is responsible for the genital anomalies, in 46,XY patients DSD results from the associated testicular dysfunction. Primary adrenal insufficiency, characterized by a reduction in cortisol secretion and overproduction of ACTH, is the rule. In addition, patients may exhibit aldosterone deficiency leading to salt-wasting crises that may be life-threatening. The trophic effect of ACTH provokes congenital adrenal hyperplasia (CAH). Adrenal steroidogenic defects leading to 46,XX DSD are 21-hydroxylase deficiency, by far the most prevalent, and 11β-hydroxylase deficiency. Lipoid Congenital Adrenal Hyperplasia due to StAR defects, and cytochrome P450scc and P450c17 deficiencies cause DSD in 46,XY newborns. Mutations in SF1 may also result in combined adrenal and testicular failure leading to DSD in 46,XY individuals. Finally, impaired activities of 3βHSD2 or POR may lead to DSD in both 46,XX and 46,XY individuals. The pathophysiology, clinical presentation and management of the above-mentioned disorders are critically reviewed, with a special focus on the latest biomarkers and therapeutic development.

scholarly journals MON-060 P-450 Oxidoreductase Deficiency with Antley Bixler Phenotype: A Novel Mutation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Anshul Kumar ◽  
Sandeep Kumar Mathur ◽  
Balram Sharma ◽  
Naincy Purwar ◽  
Himanshu sharma ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Failure To Thrive ◽  
Ambiguous Genitalia ◽  
Hydroxylase Deficiency ◽  
Left Testis ◽  
Sex Development ◽  
First Case ◽  
Midfacial Hypoplasia ◽  
Novel Variant ◽  
21 Hydroxylase Deficiency

Abstract Introduction We present first case of 46 XY Disorder of Sex Development (DSD) from India due to P-450 Oxidoreductase Deficiency with Novel variant (p.Ala541Thr) in a heterozygous state. Case Discussion 6 months old boy presented with ambiguous genitalia since birth. No history of neonatal crisis, failure to thrive and pigmentation of skin, maternal virilisation or drug ingestion during pregnancy. On examination: weight 6.2 Kg (3rd centile), height 64 cm (3rd centile), MPH-170 (25-50th centile), head circumference 38 cm (−2.7 SD), vitals stable, trigonocephaly with fused anterior and posterior fontanelle, prominent pointed forehead, midfacial hypoplasia, up slanting eyes, hypertelorism and low set ears were present. Genitalia: 1.5 cm phallus like structure with foreskin, chordee, single perineal opening in form of peno-scrotal hypospadias, bifid scrotum with poor rugosity and poor pigmentation and both gonads (1 ml) were palpable in labio-scrotal fold with external masculinization score (EMS), 6/12 and Prader stage 4. Investigations showed normal electrolytes and blood sugar, High basal ACTH, post stimulation cortisol 14mcg/dl, Basal 17-OHP was 8.6 ng/ml and post stimulation 12ng/ml, with low DHEAS 36.4 mcg/dl and androstenedione 0.42 ng/ml, LH 16.09 mIU/ml (elevated), FSH 2.97 mIU/ml (normal) and low Testosterone for his age. T/DHT 9.6 (normal&lt;10) and Testosterone /Androstenedione ratio 0.95 (normal &gt;0.8). Abdominal and Pelvic imaging showed normal adrenal glands and absent female internal genitalia, bilateral testis in labio-scrotal fold (right testis-6x6.5x11 mm, left testis-6.6x7x10 mm), corpora cavernosa and bifid scrotum. NCCT Head showed metopic craniosynostosis with trigonocephaly and hypotelorism. Skeletal survey showed bowing of femora. 20 cell Karyotype of peripheral blood lymphocyte was 46 XY. NGS was done of the POR gene, which revealed a heterozygous missense variation in exon 13 of the POR gene variant (p.Ala541Thr) which has not been reported yet. The patient was initiated hydrocortisone, fludrocortisone, DHT gel and corrective surgery is planned. Clinical learning Although in PORD classically the inheritance is generally autosomal recessive, but manifesting heterozygotes are not uncommon1. This case also shows the value of Next gen sequencing and the role it can play in DSD 1. Scott RR, Gomes LG, Huang N, Van Vliet G, Miller WL. Apparent manifesting heterozygosity in P450 oxidoreductase deficiency and its effect on coexisting 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2007;92:2318–2322

Genome analyses and androgen quantification for an infant with 5α-reductase type 2 deficiency

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Kazuhisa Akiba ◽  
Keiko Aso ◽  
Yukihiro Hasegawa ◽  
Maki Fukami
Keyword(s):  
Disorders Of Sex Development ◽  
Reference Value ◽  
Ambiguous Genitalia ◽  
Chinese Patients ◽  
Sex Development ◽  
Liquid Chromatography Tandem Mass ◽  
Exon 1 ◽  
Genome Analyses ◽  
Immune Assays

Abstract Objectives 5α-reductase type 2 deficiency due to biallelic SRD5A2 variants is a common form of 46,XY disorders of sex development. Case presentation A Chinese neonate presented with ambiguous genitalia. He carried a homozygous likely_pathogenic SRD5A2 variant (c.650C>A, p.A217E). His apparently nonconsanguineous parents were heterozygotes for the variant. The variant has previously been identified in two Chinese patients. Our patient carried 14.2 Mb loss-of-heterogeneity regions distributed in the genome. The SRD5A2 variant in this family was invariably coupled with two polymorphisms in exon 1 and intron 1. In the patient, blood testosterone (T)/5α-dihydrotestosterone (5αDHT) ratios were elevated before and during mini puberty, and were higher when measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) than measured by conventional immune assays. Conclusions This study provides evidence for the founder effect of an SRD5A2 variant. Furthermore, our data indicate that there is a need to establish a new reference value for T/5αDHT ratios using LC-MS/MS.

Disorders of sex development

2017 ◽  
Author(s):  
David F.M. Thomas
Keyword(s):  
Disorders Of Sex Development ◽  
Ambiguous Genitalia ◽  
Surgical Reconstruction ◽  
Adrenal Hyperplasia ◽  
Specialist Care ◽  
Gender Assignment ◽  
Developmental Abnormalities ◽  
Sex Development

The aetiology of disorders of sex development (DSD) is multifactorial and includes chromosomal defects, developmental abnormalities of the gonads, and defects of hormonal synthesis and expression. Infants born with ambiguous genitalia require urgent investigation because of the risk of hyponatraemia associated with congenital adrenal hyperplasia (CAH) and to permit an informed decision on gender assignment. CAH is the commonest form of DSD, accounting for around 80% of all infants born with ambiguous genitalia. Despite controversy regarding timing and consent, feminizing genitoplasty in early childhood remains the accepted management for girls with significant clitoromegaly. Surgical reconstruction for 46XY DSD is guided by several factors, notably the size of the phallus and gonadal phenotype. The majority of individuals with disorders of sex development will require ongoing specialist care and long-term multidisciplinary follow-up and support.

scholarly journals Etiology and Clinical Presentation of Disorders of Sex Development in Kenyan Children and Adolescents

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Prisca Amolo ◽  
Paul Laigong ◽  
Anjumanara Omar ◽  
Stenvert Drop
Keyword(s):  
Children And Adolescents ◽  
Sex Chromosome ◽  
Clinical Laboratory ◽  
Molecular Genetic ◽  
Management Strategies ◽  
Disorders Of Sex Development ◽  
Ambiguous Genitalia ◽  
Molecular Genetic Analysis ◽  
High Rate ◽  
Sex Development

Objective. The purpose of this study was to describe baseline data on etiological, clinical, laboratory, and management strategies in Kenyan children and adolescents with Disorders of Sex Development (DSD). Methods. This retrospective study included patients diagnosed with DSD who presented at ages 0–19 years from January 2008 to December 2015 at the Kenyatta National (KNH) and Gertrude’s Children’s (GCH) Hospitals. After conducting a search in the data registry, a structured data collection sheet was used for collection of demographic and clinical data. Data analysis involved description of the frequency of occurrence of various variables, such as etiologic diagnoses and patient characteristics. Results. Data from the records of 71 children and adolescents were reviewed at KNH (n = 57, 80.3%) and GCH (n = 14, 19.7%). The mean age at the time of diagnosis was 2.7 years with a median of 3 months. Thirty-nine (54.9%) children had karyotype testing done. The median age (IQR) of children with reported karyotypes and those without was 3.3 years (1.3–8.9) and 8.3 years (3.6–12.1), respectively (p=0.021). Based on karyotype analysis, 19 (48.7%) of karyotyped children had 46,XY DSD and 18 (46.2%) had 46,XX DSD. There were two (5.1%) children with sex chromosome DSD. Among the 71 patients, the most common presumed causes of DSD were ovotesticular DSD (14.1%) and CAH (11.3%). Majority (95.7%) of the patients presented with symptoms of DSD at birth. The most common presenting symptom was ambiguous genitalia, which was present in 66 (93.0%) patients either in isolation or in association with other symptoms. An ambiguous genitalia was initially observed by the patient’s mother in 51.6% of 62 cases despite the high rate (84.7%) of delivery in hospital. Seventeen (23.9%) of the cases had a gender reassignment at final diagnosis. A psychologist/psychiatrist or counselor was involved in the management of 23.9% of the patients. Conclusion. The commonest presumed cause of DSD was ovotesticular DSD in contrast to western studies, which found CAH to be more common. Investigation of DSD cases is expensive and needs to be supported. We would have liked to do molecular genetic analysis outside the country but financial challenges made it impossible. A network for detailed diagnostics in resource-limited countries would be highly desirable. There is a need to train health care workers and medical students for early diagnosis. Psychological evaluation should be carried out for all patients at diagnosis and support given for families.

scholarly journals Novel phenotypes and genotypes in Antley-Bixler syndrome caused by cytochrome P450 oxidoreductase deficiency: based on the first cohort of Chinese children

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Lijun Fan ◽  
Xiaoya Ren ◽  
Yanning Song ◽  
Chang Su ◽  
Junfen Fu ◽  
...  
Keyword(s):  
Lower Eyelid ◽  
Chinese Children ◽  
Hydroxylase Deficiency ◽  
Craniofacial Malformations ◽  
Genetic Characteristics ◽  
P450 Oxidoreductase ◽  
Sex Development ◽  
Skeletal Malformations ◽  
Novel Variants ◽  
21 Hydroxylase Deficiency

Abstract Background Antley-Bixler syndrome (ABS) caused by P450 oxidoreductase deficiency (PORD) is a congenital adrenal hyperplasia with skeletal malformations and disordered sex development in both sexes. There have been no reports of ABS caused by PORD in Chinese children. Methods We described the clinical and genetic characteristics of eight Chinese children with ABS caused by PORD and compared them with those of subjects in previous studies. Results Eight patients, aged 6 months–17.8 years, showed strikingly similar craniofacial malformations. We first described four unreported features: lower eyelid fat pads (4/8), prominent lower eyelid-zygoma transverse line (4/8), underdeveloped or absent antihelix (5/8) and single earlobe crease (5/8). Five 46, XY patients presented various degrees of undervirilization, while three 46, XX cases showed masculinization. Basal endocrine measurements revealed the following consistent results: normal cortisol; elevated adrenocorticotropic hormone, progesterone, pregnenolone, 17-hydroxypropgesterone, and corticosterone; and decreased or normal testosterone/oestradiol. We identified three previously reported variants and four novel variants (c.51719_51710delGGCCCCTGTGinsC, p.D210G, p.Y248X and p.R554X) of POR. The most prevalent variant was p.R457H (8/16). The hydrocortisone dosages of patients differed because of variable degrees of adrenal insufficiency. Conclusions We described novel phenotypes and genotypes of ABS caused by PORD. The variant p.R457H was the most prevalent in this cohort. All subjects had combined characteristics of 17-hydroxylase and 21-hydroxylase deficiency. Steroid replacement therapy for patients with PORD requires individually tailored dosing.

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