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2019-01-25

Sexual Identity Disorder and Psychosis in Klinefelter Syndrome: A Synthesis of Literature and a Case Report.

J Nerv Ment Dis. 2019 Jan 21. doi: 10.1097/NMD.0000000000000930. [Epub ahead of print]

Sexual Identity Disorder and Psychosis in Klinefelter Syndrome: A Synthesis of Literature and a Case Report.

Maillefer A1, Sabe M1, Coste C1, Bartolomei J1, Jaafar J2, Sentissi O1.

Author information スイス


Abstract

Klinefelter syndrome (KS) 47, XXY is the most frequent chromosomal abnormality causing hypogonadism in humans. This chromosomal abnormality of number in its classical form called homogeneous (supernumerary X) is generally the result of a meiosis accident. Several studies have suggested that individuals with KS are at greater risk of developing various psychiatric disorders, including depression and schizophrenia. The diagnosis is made based on subnormal testosterone with high pituitary gonadotropins and confirmed by determining the karyotype on a blood simple. We did a literature review using an electronic search in three databases: Pubmed/MEDLINE, Google Scholar, and PsychInfo. We found that since 1989, seven case reports with KS and mental disorders with similar and different characteristics of our case illustration of a patient with KS and psychosis were published.

2019-01-19

The Association of Motor Skills and Adaptive Functioning in XXY/Klinefelter and XXYY Syndromes.

Phys Occup Ther Pediatr. 2018 Dec 28:1-14. doi: 10.1080/01942638.2018.1541040. [Epub ahead of print]

The Association of Motor Skills and Adaptive Functioning in XXY/Klinefelter and XXYY Syndromes.

Martin S1,2, Cordeiro L3, Richardson P2, Davis S3, Tartaglia N1,3.

Author information アメリカ


Abstract

AIMS:

Klinefelter (XXY) and XXYY syndromes are genetic disorders in males characterized by additional sex chromosomes compared to the typical male karyotype of 46, XY. Both conditions have been previously associated with motor delays and motor skills deficits. We aimed to describe and compare motor skills in males with XXY and XXYY syndromes, and to analyze associations with age, cognitive abilities, and adaptive functioning.

METHODS:

Sixty-four males with XXY and 46 males with XXYY, ages 4-20 were evaluated using the Beery Test of Visual Motor Integration and the Bruininks-Oseretsky Test of Motor Proficiency - 2nd Edition assessments, Vineland-2 adaptive scales, and cognitive testing.

RESULTS:

Motor coordination impairments were found in 39% of the males with XXY and 73% of the males with XXYY. Both groups showed strengths in visual perceptual skills. Males with XXYY had lower mean scores compared to males with XXY across all assessments. Fine motor dexterity and coordination deficits were common. There was a positive correlation between VMI scores and adaptive functioning.

CONCLUSION:

Occupational and physical therapists should be aware of the motor phenotype in XXY and XXYY both to aid in diagnosis of unidentified cases and to guide intervention.


KEYWORDS:

47; Klinefelter syndrome; activities of daily living; motor skills; occupational therapy; physical therapy; visual motor integration; xxy; xxyy

High-level language competencies and Theory of Mind in a group of children with Klinefelter syndrome.

Am J Med Genet A. 2019 Jan 8. doi: 10.1002/ajmg.a.12. [Epub ahead of print]

High-level language competencies and Theory of Mind in a group of children with Klinefelter syndrome.

Melogno S1,2, Pinto MA1, Badolato F3, Sist E1, Esposito A3, Orsolini M1, Tarani L3.

Author information イタリア


Abstract

Klinefelter syndrome (KS) is a genetic anomaly involving the presence of one or more supernumerary X chromosomes in male individuals. In the cognitive profile of these individuals, strengths are found in nonverbal abilities, whereas weaknesses are observed in executive function, language, and academic performance. Our study is based on a comparison between eight children diagnosed with KS (47,XXY) (age range: 9-13 years; IQ range: 80-123), with no delay in language development, and eight typically developing (TD) controls. We explored a range of high-level language competencies and Theory of Mind (ToM) in addition to basic language competency. High-level language competencies were assessed by a battery that measures pragmatic language skills and a metaphor comprehension test (MCT). To assess ToM, we administered the corresponding subtest of the NEPSY II. Basic language competence was assessed by the NEPSY II Comprehension of Instructions subtest. Although basic language performance did not differentiate the individuals with KS from the TD controls, relevant differences appeared in some of the high-level language competencies as well as in the ToM task. All tasks in which the individuals with KS performed less well were characterized by complex inferential processes. Some possible clinical and educational implications are discussed.

© 2019 Wiley Periodicals, Inc.


KEYWORDS:

High-level language competencies; Klinefelter syndrome; Theory of Mind; Verbal inferential processes; metaphor comprehension

The incidence of anxiety symptoms in boys with 47,XXY (Klinefelter syndrome) and the possible impact of timing of diagnosis and hormonal replacement therapy.

Am J Med Genet A. 2019 Jan 13. doi: 10.1002/ajmg.a.61038. [Epub ahead of print]

The incidence of anxiety symptoms in boys with 47,XXY (Klinefelter syndrome) and the possible impact of timing of diagnosis and hormonal replacement therapy.

Samango-Sprouse C1,2,3,4, Lasutschinkow P4, Powell S1, Sadeghin T4, Gropman A1,2.

Author information アメリカ

Abstract

47,XXY (Klinefelter syndrome) is the most common X and Y chromosomal variation (1:660 males). The incidence of anxiety disorders and the impact of hormonal replacement therapy (HRT) is not well understood. Child Behavior Checklist and Screen for Childhood Anxiety Related Emotional Disorders were completed by parents of 80 boys with 47,XXY. Forty received HRT prior to 10 years of age while 40 did not. HRT (22.5%) received early hormonal treatment prior to 18 months. About 32.5% received hormone booster treatment between 5 and 10 years. The remaining 42.5% received both. There were fewer reported social (p = .015), thought (p = .012), and affective problems (p = .048) in treated boys when compared to untreated. Boys with both treatments demonstrated fewer symptoms on anxious/depressed scale (p = .001) compared to those with early treatment only. Within the treated group, prenatally diagnosed showed fewer indications of anxiety problems (p = .02) than their postnatal counterparts. This comparative, cross-sectional study expands previous findings on the possible positive effect of HRT in boys with 47,XXY. Anxiety disorders appear to be a penetrant aspect of the 47,XXY phenotype. Further investigation is warranted to explore the relationship between biological treatment and individual responses to HRT to develop more personalized and precise medicine.

© 2019 Wiley Periodicals, Inc.


KEYWORDS:

47,XXY; Klinefelter syndrome; X and Y chromosomal variations; anxiety disorders; hormonal replacement therapy; sex chromosome abnormalities and aneuploidies

2019-01-04

The Sexual Differentiation of the Human Brain: Role of Sex Hormones Versus Sex Chromosomes.

Curr Top Behav Neurosci. 2019 Jan 1. doi: 10.1007/7854_2018_70. [Epub ahead of print]

The Sexual Differentiation of the Human Brain: Role of Sex Hormones Versus Sex Chromosomes.

Bakker J1.

Author information
1Laboratory of Neuroendocrinology, GIGA Neurosciences, Liège University, Liège, Belgium. jbakker@uliege.be.

Abstract

Men and women differ, not only in their anatomy but also in their behavior. Research using animal models has convincingly shown that sex differences in the brain and behavior are induced by sex hormones during a specific, hormone-sensitive period during early development. Thus, male-typical psychosexual characteristics seem to develop under the influence of testosterone, mostly acting during early development. By contrast, female-typical psychosexual characteristics may actually be organized under the influence of estradiol during a specific prepubertal period. The sexual differentiation of the human brain also seems to proceed predominantly under the influence of sex hormones. Recent studies using magnetic resonance imaging have shown that several sexually differentiated aspects of brain structure and function are female-typical in women with complete androgen insensitivity syndrome (CAIS), who have a 46 XY karyotype but a female phenotype due to complete androgen resistance, suggesting that these sex differences most likely reflect androgen action, although feminizing effects of estrogens or female-typical socialization cannot be ruled out. By contrast, some male-typical neural characteristics were also observed in women with CAIS suggesting direct effects of sex chromosome genes in the sexual differentiation of the human brain. In conclusion, the sexual differentiation of the human brain is most likely a multifactorial process including both sex hormone and sex chromosome effects, acting in parallel or in combination.

男性と女性は、解剖学的構造だけではなく行動も異なる。動物モデルを用いた研究は、脳内の性差および行動が、初期の発達中の特定のホルモン感受性期間中に性ホルモンによって誘発されることと納得されることが示されている。このように、男性特有の精神的性的特徴はテストステロンの影響下で発達し、大部分は初期発達中に作用しているように思われる。それとは対照的に、女性特有の精神的性的特徴は、実際には特定の思春期前の期間中にエストラジオールの影響下で組織化されているかもしれません。人間の脳の性分化も性ホルモンの影響下で主に進行するようである。磁気共鳴画像法を用いた最近の研究は、46のXY核型を有するが完全なアンドロゲン耐性のために女性の表現型を有する完全型アンドロゲン不応症(CAIS)の女性において脳の構造および機能のいくつかの性分化側面が女性特有であることが示された。これらの性差はアンドロゲン作用を反映している可能性が最も高いが、エストロゲンの女性化効果または女性特有の社会化は排除できない。これとは対照的に、CAISの女性でも男性特有の神経特性がいくつか観察され、これはヒト脳の性分化における性染色体遺伝子の直接的な影響を示唆している。結論として、人間の脳の性分化は、性ホルモン効果と性染色体効果の両方を含む多因子プロセスであり、並行してまたは組み合わせて作用する可能性が最も高い。


KEYWORDS:
Androgens; Brain function; Brain structure; Complete androgen insensitivity syndrome; Estrogens; Magnetic resonance imaging; Sex differences; Sexual development

Two Korean girls with complete androgen insensitivity syndrome diagnosed in infancy.

Ann Pediatr Endocrinol Metab. 2018 Dec;23(4):220-225. doi: 10.6065/apem.2018.23.4.220. Epub 2018 Dec 31.

Two Korean girls with complete androgen insensitivity syndrome diagnosed in infancy.

Heo YJ1, Ko JM1,2, Lee YA1, Shin CH1, Yang SW1, Kim MJ3, Park SS3.

Author information 韓国

Abstract

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent Müllerian duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.

KEYWORDS:
Androgen receptors; Disorders of sexual development; Androgen-insensitivity syndrome

出生時にヘルニアにて判明したケース

Partial androgen insensitivity syndrome presenting as pubertal gynecomastia: clinical and hormonal findings and a novel mutation in the androgen receptor gene.

Endocrinol Diabetes Metab Case Rep. 2018 Dec 28;2018. pii: EDM180128. doi: 10.1530/EDM-18-0128. [Epub ahead of print]

Partial androgen insensitivity syndrome presenting as pubertal gynecomastia: clinical and hormonal findings and a novel mutation in the androgen receptor gene.

Vaidyanathan P1, Kaplowitz P1.

Author information
1Division of Endocrinology, Children's National Health System, Washington, District of Columbia, USA.

Abstract

Pubertal gynecomastia is common, can be seen in 65% of the adolescent boys and is considered physiological. It is thought to be due to transient imbalance between the ratio of testosterone and estradiol in the early stages of puberty. It resolves in 1-2 years and requires no treatment. However, more persistent and severe pubertal gynecomastia is less common and can be associated with pathological disorders. These can be due to diminished androgen production, increased estrogen production or androgen resistance. We report a case of persistent pubertal gynecomastia due to partial androgen insensitivity syndrome (PAIS), classical hormone findings and a novel mutation in the androgen receptor (AR) gene. Learning points: Laboratory testing of follicle-stimulating hormone (FSH), leutinizing hormone (LH) and testosterone for pubertal gynecomastia is most helpful in the setting of undervirization. The hormonal finding of very high testosterone, elevated LH and estradiol and relatively normal FSH are classical findings of PAIS. Gynecomastia due to PAIS will not resolve and surgery for breast reduction should be recommended.

Learning points:
•Laboratory testing of follicle-stimulating hormone (FSH), leutinizing hormone (LH) and testosterone for pubertal gynecomastia is most helpful in the setting of undervirization.
•The hormonal finding of very high testosterone, elevated LH and estradiol and relatively normal FSH are classical findings of PAIS.
•Gynecomastia due to PAIS will not resolve and surgery for breast reduction should be recommended.




KEYWORDS:
2018; Adolescent/young adult; Androgen insensitivity syndrome; Black - African ; Chromosomal analysis; December; FSH; Genetics and mutation; Gynaecomastia; LH; Male; Mastectomy; Molecular genetic analysis; Oestradiol (E2); Paediatrics; Tanner scale; Testes; Testosterone; Unique/unexpected symptoms or presentations of a disease; United States; Virilisation (abnormal)

2018-12-30

Pregnancy in patient with Swyer syndrome.

Fertil Steril. 2011 Apr;95(5):1789.e1-2. doi: 10.1016/j.fertnstert.2010.12.012. Epub 2010 Dec 31.

Pregnancy in patient with Swyer syndrome.

Tulic I1, Tulic L, Micic J.

Author information セルビア

Abstract

OBJECTIVE:
To report a case of successful pregnancy and delivery after IVF and ET in a patient with Swyer syndrome.

DESIGN:
Case report.

SETTING:
Unit of Assisted Reproduction, Gynecology and Obstetrics Institute, University of Belgrade.

PATIENT(S):
A 30-year-old patient with 46,XY gonadal dysgenesis.

INTERVENTION(S):
Chromosomal analysis, diagnostic laparoscopy, IVF using donor oocytes, ET, and cesarean delivery.

MAIN OUTCOME MEASURE(S):
Successful pregnancy and live birth.

RESULT(S):
Successful treatment, pregnancy, and delivery.

CONCLUSION(S):
A patient with 46,XY gonadal dysgenesis in a donor oocyte program, can maintain a normal pregnancy and delivery.




Swyer was the first one to describe 46 gonadal dysgenesis, and the syndrome may be expressed either in a complete or incomplete form. Characteristics of a fully expressed syndrome are as follows: female phenotype, either normal or tall stature, bilateral gonadal dysgenesis, and sexual infantilism with primary amenorrhea and eunuchoid habitus. The phenotype is completely female, with existing tubes, vagina, and various grades of uterus hypoplasia ranging from severe to mild underdevelopment.

Dysgenesis-related streak gonads appear in 30%–40% cases of patients with primary amenorrhea. The prevalence of ovarian insufficiency in women with primary amenorrhea varies between 10% and 28% (1).
Case report

The report refers to a female patient, age 30, who was diagnosed with Swyer syndrome at the age of 19; the diagnosis was made by an endocrinologist. The patient underwent detailed examination for the cause of primary amenorrhea. She was of a female phenotype, of eumetabolic state, tall stature, and eunochoid proportion: lower trunk: 111 cm, extended arm distance 190 cm, undeveloped breasts, and grade 2 axillary hair. Thyroid gland was within physiological limits. She had female external genitalia and female body hair (grade II–III) and no evidence of clitoromegaly. Psychologically, the patient was clearly defined as a female. Pelvic ultrasound revealed an extremely hypoplastic uterus with the largest sagittal diameter of 30 mm. Ovaries were unavailable for exploration. Ultrasound examination of breasts revealed bilaterally a rather deficient fibroglandular component. Gynecological examination confirmed female genitalia with normal characteristics and normal vagina. The uterus was not differentiated, and the adnexa were not palpable. Pelvis computed tomography showed a hypoplastic uterus of 30 mm in diameter. No soft tissue mass of ovarian origin was detected in the bilateral adnexal area. Laparoscopic examination revealed a 30 mm diameter uterus out of which extended hypoplastic tubes of preserved ampulla-infundibulum segments of distinct fimbrials. Whitish fibrotic changes were noticed at the site of the missing ovaries.

Her karyotype was 46,XY. Genetic analyses of the SRY and ATL1 genes were performed, and SRY I ATL1 gene expression was confirmed by multiplex polymerase chain reaction in genomic DNA. Direct sequencing on genomic DNA in both directions did not reveal a mutation in the SRY gene.

Hormone levels were as follows: low-normal cortisol level (220 nmol/L), high levels of gonadotropin (FSH, 176.4 mIU/L; LH, 26.9 mIU/L), nonmeasurable E2 (0.02 pmol/L), T within normal limits (1/72 nmol/L), and PRL within normal limits (184.2 mIU/L). Tumor markers and alfa-fetoprotein (1.36 ng/mL) and β-hCG (<1.0 mIU/mL) were within normal limits.

The patient has been undergoing replacement therapy since the age of 19. Among other things, the growth and development of the uterus itself were monitored. When the patient was at the age of 29, vaginal ultrasound examination showed uterine dimensions as follows: uterine longitudinal diameter 60 mm, anteroposterior diameter 25 mm, and transversal diameter 35 mm. The patient was introduced to the oocyte donation program. Her cousin was the oocyte donor. The donor underwent the controlled ovarian stimulation through a long protocol. Recipient treatment consisted of stimulation of GnRH and estrogen as per the scheme of Styne-Gross et al. (2). Five donated oocytes were inseminated with processed sperm of the recipient’s husband. On the second day, three embryos of the four-blastomere stage were returned using the ultrasound control. The level of serum β-hCG was 230 mIU/mL on the 14th day after ET. Four weeks after ET, during ultrasound examination, intrauterine presence of a gestational sac was noted; 2 weeks later, there was a fetus with registered heart action. The pregnancy was continuously monitored. A healthy baby with an Apgar score of 9 was delivered by cesarean section at the 39th week of gestation. The cesarean delivery was performed owing to breech presentation and reduced amniotic fluid.
Discussion

Swyer syndrome was originally described in 1955 in two women with primary amenorrhea, with normal appearance of external genitalia and normal vagina but with hypoplastic uterus and gonads localized at the place where ovaries are commonly positioned. These women were of tall stature, minimally developed breasts, normal pubic and axillary hair, normal vagina and cervix, small uterus, and no palpable adnexal structures. Swyer syndrome implies no match between genotype-phenotype correlations. Phenotype is female and genotype is male (3). It is commonly detected at the age of 18–23 owing to primary amenorrhea (4, 5). Risks of gonadal dysgenesis include prolonged hypoestrogenemia with osteoporosis, virilization and a high risk of gonadal neoplasia; therefore, early prophylactic removal of the dysgenetic gonads is recommended. For hypoestrogenemia, cycle regulation, and beneficial psychological effect, hormone replacement therapy is essential. The presence of the XY genotype and H-Y antigen does not affect normal uterine and endometrial response, and the possibility of maintaining a normal pregnancy and delivery confirms the physiological ability of the uterus to accommodate and maintain a successful pregnancy in patients with XY dysgenesis (6). However, the literature reports fewer than 12 full-term pregnancies in patients with Swyer syndrome (7, 8, 9, 10, 11, 12, 13, 14). It is quite clear that we need reports on pregnancy outcomes in patients with Swyer syndrome to expand our knowledge and define better any specific risks in this unique patient population. As in our case, most pregnancies in patients with Swyer syndrome necessitated cesarean section owing to a number of indications. Despite some opinions that androgenic pelvic shape in Swyer syndrome patients may indicate a possible abnormal delivery, causes of the high prevalence of cesarean sections is still unclear.

2018-12-26

Sexual experience before treatment for vaginal agenesis: a retrospective review of 137 women.

J Pediatr Adolesc Gynecol. 2018 Dec 21. pii: S1083-3188(18)30387-5. doi: 10.1016/j.jpag.2018.12.005. [Epub ahead of print]

Sexual experience before treatment for vaginal agenesis: a retrospective review of 137 women.

Dear J1, Creighton SM1, Conway GS1, Williams L1, Liao LM2.

Author information イギリス
1Women's Health Division, University College London Hospitals NHS Foundation Trust, Second Floor North, 250 Euston Road, London NW1 2PG, UK.
2Women's Health Division, University College London Hospitals NHS Foundation Trust, Second Floor North, 250 Euston Road, London NW1 2PG, UK. Electronic address: lih-mei.liao@nhs.net.

Abstract

STUDY OBJECTIVE:

To summarise the self-reported sexual experiences of women with vaginal agenesis before treatment and interpret the clinical implications.

DESIGN:

A retrospective review of pre-treatment baseline sexuality data and medical records of women with vaginal agenesis seeking vaginal construction.

SETTING:

A specialist multidisciplinary centre for women with complex congenital genital anomalies.

PARTICIPANTS:

137 women with untreated vaginal agenesis associated with Complete Androgen Insensitivity Syndrome (CAIS) and Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH) aged 15 to 41 years (mean 20 years).

METHODS:

Gynecological examination and completion of questionnaires.

OUTCOME MEASURES:

1) Sexual Experiences Questionnaire (SEQ); 2) Multi-dimensional Sexuality Questionnaire (MSQ); 3) Vaginal Self-Perceptions; 4) Vaginal length.

RESULTS:

A sizable proportion of women reported having had sexually intimate experiences before any intervention on the vagina. Vaginal length, which ranged from dimple to 7 cm and averaged 2.7cm for the cohort, was unrelated to the range of sexual experiences. Although most women perceived their vagina as being too small, less than half felt that a sexual partner would notice. Two thirds subsequently completed the dilation programme, which was not predicted by pre-treatment vaginal length or sexual experience.

CONCLUSION:

Contrary to the assumption that a vagina of certain dimensions is a pre-requisite for women to 'have sex,' many women with MRKHS and CAIS reported having experienced genital and non-genital sexual activities without treatment. Treatment providers could helpfully affirm women's capacity for sexual intimacy, relationships and enjoyment before introducing the topic of vaginal construction as a non-urgent choice.

Copyright © 2018. Published by Elsevier Inc.

KEYWORDS:
CAIS; Clinical psychology; DSD; Intersex; MRKHS; Multi-dimensional Sexuality Questionnaire; Sexual Experience Questionnaire; Sexual Health; Vaginal Agenesis; Vaginal Dilation