-
International Journal of Women's... Oct 2023Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal,... (Review)
Review
BACKGROUND
Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal, or anatomic sex.
OBJECTIVE
Dermatologic care is an important component of the multidisciplinary care needed for individuals with DSD. This article discusses the most common primary dermatologic manifestations of DSD in addition to the cutaneous manifestations of hormonal and surgical therapies in individuals with DSD.
DATA SOURCES
Published articles including case series and case reports on PubMed.
STUDY SELECTIONS
Selection was conducted by examining existing literature with a team of multidisciplinary specialists.
METHODS
Narrative review.
LIMITATIONS
This article was not conducted as a systematic review.
RESULTS
In Klinefelter syndrome, refractory leg ulcers and incontinentia pigmenti have been described. Turner syndrome is associated with lymphatic malformations, halo nevi, dermatitis, and psoriasis. Virilization can be seen in some forms of congenital adrenal hyperplasia, where acne and hirsutism are common.
CONCLUSION
Dermatologists should consider teratogenic risk for treatments of skin conditions in DSD depending on pregnancy potential. Testosterone replacement, commonly used for Klinefelter syndrome, androgen insensitivity syndrome, 5-alpha reductase deficiency, gonadal dysgenesis, or ovotesticular DSD, may cause acne.
PubMed: 37671254
DOI: 10.1097/JW9.0000000000000106 -
Frontiers in Endocrinology 2024Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which... (Review)
Review
Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which otherwise give rise to the Fallopian tubes, the uterus and the upper part of the vagina. In the first trimester of fetal life, AMH is expressed independently of gonadotropins, whereas from the second trimester onwards AMH testicular production is stimulated by FSH and oestrogens; at puberty, AMH expression is inhibited by androgens. AMH has also been suggested to participate in testicular descent during fetal life, but its role remains unclear. Serum AMH is a well-recognized biomarker of testicular function from birth to the first stages of puberty. Especially in boys with nonpalpable gonads, serum AMH is the most useful marker of the existence of testicular tissue. In boys with cryptorchidism, serum AMH levels reflect the mass of functional Sertoli cells: they are lower in patients with bilateral than in those with unilateral cryptorchidism. Interestingly, serum AMH increases after testis relocation to the scrotum, suggesting that the ectopic position result in testicular dysfunction, which may be at least partially reversible. In boys with cryptorchidism associated with micropenis, low AMH and FSH are indicative of central hypogonadism, and serum AMH is a good marker of effective FSH treatment. In patients with cryptorchidism in the context of disorders of sex development, low serum AMH is suggestive of gonadal dysgenesis, whereas normal or high AMH is found in patients with isolated androgen synthesis defects or with androgen insensitivity. In syndromic disorders, assessment of serum AMH has shown that Sertoli cell function is preserved in boys with Klinefelter syndrome until mid-puberty, while it is affected in patients with Noonan, Prader-Willi or Down syndromes.
Topics: Female; Humans; Male; Anti-Mullerian Hormone; Cryptorchidism; Androgens; Follicle Stimulating Hormone; Peptide Hormones
PubMed: 38501100
DOI: 10.3389/fendo.2024.1361032 -
Ginekologia Polska Feb 2024Congenital malformations of the female genital organs are rare anomalies and their incidence is estimated to be up to 7% in the general population. Müllerian ducts...
Congenital malformations of the female genital organs are rare anomalies and their incidence is estimated to be up to 7% in the general population. Müllerian ducts abnormalities are one of the causes of infertility and occur in approximately 16% of women with recurrent miscarriages. Sex development disorders are diagnosed at different stages of the patient's life depending on the accompanying ailments. Alarming signs of genital malformations include primary amenorrhea or dysmenorrhea, dyspareunia, and periodic abdominal pain.
PubMed: 38334344
DOI: 10.5603/gpl.97034 -
PloS One 2023Almost 40% of infertile men cases are classified as idiopathic when tested negative to the current diagnostic routine based on the screening of karyotype, Y chromosome...
Almost 40% of infertile men cases are classified as idiopathic when tested negative to the current diagnostic routine based on the screening of karyotype, Y chromosome microdeletions and CFTR mutations in men with azoospermia or oligozoospermia. Rare monogenic forms of infertility are not routinely evaluated. In this study we aim to investigate the unknown potential genetic causes in couples with pure male idiopathic infertility by applying variant prioritization to whole exome sequencing (WES) in a cohort of 99 idiopathic Italian patients. The ad-hoc manually curated gene library prioritizes genes already known to be associated with more common and rare syndromic and non-syndromic male infertility forms. Twelve monogenic cases (12.1%) were identified in the whole cohort of patients. Of these, three patients had variants related to mild androgen insensitivity syndrome, two in genes related to hypogonadotropic hypogonadism, and six in genes related to spermatogenic failure, while one patient is mutant in PKD1. These results suggest that NGS combined with our manually curated pipeline for variant prioritization and classification can uncover a considerable number of Mendelian causes of infertility even in a small cohort of patients.
Topics: Humans; Male; Exome; Infertility, Male; Azoospermia; Oligospermia; Mutation
PubMed: 37540677
DOI: 10.1371/journal.pone.0288336 -
Cureus Feb 2024Androgen insensitivity syndrome is a rare X-linked recessive condition in which patients present a female phenotype. After complete androgen insensitivity syndrome...
Androgen insensitivity syndrome is a rare X-linked recessive condition in which patients present a female phenotype. After complete androgen insensitivity syndrome (CAIS) diagnosis, the timing of gonadectomy should be evaluated, considering the risks and benefits of this procedure. This paper reports an uncommon case of complete androgen insensitivity syndrome diagnosed belatedly in an adult patient. Surgical treatment was deemed necessary due to the elevated risk of gonadal malignancy.
PubMed: 38516495
DOI: 10.7759/cureus.54550 -
Cureus Jun 2023Ambiguous genitalia is a matter of concern and needs thorough evaluation and treatment. Gonadectomy becomes a potentially lifesaving procedure in patients with partial...
Ambiguous genitalia is a matter of concern and needs thorough evaluation and treatment. Gonadectomy becomes a potentially lifesaving procedure in patients with partial androgen insensitivity due to the increased risk of malignancy if left undiagnosed. We present a case report of two patients in their late 20s and 30s, raised as girls, who came with complaints of primary amenorrhea with ambiguous genitalia. Both patients had features of masculinization. Her MRI revealed an absent uterus, cervix, upper 2/3 of the vagina, and ovaries, with the presence of bilateral testicles. She was diagnosed with partial androgen insensitivity syndrome. The first patient underwent bilateral gonadectomy with hernia repair and nerve-sparing reduction clitoroplasty with labioplasty. She is under close follow-up with a further plan for augmentation mammoplasty. The second patient, however, refused clitoroplasty and underwent bilateral gonadectomy. Androgen insensitivity syndrome is an X-linked inheritance with a mutation in the AR gene. It consists of a spectrum of conditions ranging from complete insensitivity to less insensitivity towards testosterone, which results in a complete, partial, and mild form of androgen insensitivity syndrome. Studies have been done on cosmetic outcomes after genitoplasty in children with genital atypicalities, which showed significant improvement (p<0.001) and no difference in ratings by parents and surgeons. Surgeries done on patients with partial androgen insensitivity syndrome are not only lifesaving procedures, but with reasonable reassurance, these aesthetic surgeries help people live a life that otherwise would have been genetically compromised.
PubMed: 37485217
DOI: 10.7759/cureus.41142 -
Annals of Pediatric Endocrinology &... Sep 2023Androgen insensitivity syndrome (AIS) is a rare X-linked recessive disorder caused by unresponsiveness to androgens because of mutations in the AR gene. Here, we...
PURPOSE
Androgen insensitivity syndrome (AIS) is a rare X-linked recessive disorder caused by unresponsiveness to androgens because of mutations in the AR gene. Here, we investigated the clinical outcomes and molecular spectrum of AR variants in patients with AIS attending a single academic center.
METHODS
This study included 19 patients with AIS who were confirmed by molecular analysis of AR. Clinical features and endocrinological findings were retrospectively collected, including presenting features, external genitalia, sex of rearing, timing of gonadectomy, pubertal outcomes, and sex hormone levels. Molecular analysis of AR was performed using Sanger, targeted gene panel, or whole-exome sequencing.
RESULTS
Among all 19 patients, 14 (74%) were classified as having complete AIS (CAIS), whereas 5 (26%) had partial AIS (PAIS). All patients with CAIS, and 3 patients with PAIS were reared as female. One patient with CAIS manifested a mixed germ cell tumor at the age of 30 years. Molecular analysis of AR identified 19 sequence variants; 12 (63%) were previously reported, and the remaining 7 (37%) were novel. Missense mutations were the most common type (12 of 19, 63%), followed by small deletions, nonsense mutations, an insertion, and a splice site mutation.
CONCLUSION
Here, we describe the clinical outcomes and molecular characteristics of 19 Korean patients with AIS. Patients with PAIS manifested various degrees of masculinization of the external genitalia. Nonsense and frameshift mutations were frequent in patients with CAIS, whereas patients with PAIS harbored exclusively missense mutations.
PubMed: 36731508
DOI: 10.6065/apem.2244152.076