A Klinefelter boy with congenital adrenal hyperplasia: too much or too little androgens?

Zanella, Giada; Tornese, Gianluca; Mascheroni, E.; Faleschini, Elena; Ventura, Alessandro; Barbi, Egidio

doi:10.1186/s13052-018-0485-x

Cited by 4 publications

(6 citation statements)

References 10 publications

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“…He was found to have karyotype 47XXY, and a post hoc molecular analysis showed that a pathogenic variant in HSD3B2 and not CYP21A2 was the cause of the disease. The association of Klinefelter syndrome and CAH is extremely rare, with very few cases reported in the literature [ [39] , [40] , [41] ]. More details of this case will be presented in a future manuscript.…”

Section: Discussionmentioning

confidence: 99%

CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica

Umaña-Calderón

Acuña-Navas

Alvarado

et al. 2021

Molecular Genetics and Metabolism Reports

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Steroid 21-hydroxylase deficiency accounts for 95% of congenital adrenal hyperplasia (CAH) cases. Newborn screening has allowed for early detection of the disease, and currently, molecular analysis can identify the genotypes of these patients. Phenotype-genotype correlation has been well described in previous studies. In Costa Rica, there is no data about the genetic background of these patients, nor their phenotypic correlation. Design Observational, retrospective, descriptive study based on the review of patient records who had a diagnosis of CAH and were performed molecular analysis using gene sequencing or MLPA during the period from 2006 to 2018 ( N = 58). Objective To describe the clinical and genetic characteristics of CAH patients due to 21-hydroxylase deficiency at the National Children's Hospital “Dr. Carlos Sáenz Herrera”, Caja Costarricense de Seguro Social (CCSS) in Costa Rica. Results 53% (31/58) of the patients were male and 80% (37/46) were born full term; 72% (42/58) had salt wasting phenotype, 9% (5/58) simple virilizing phenotype and 19% (11/58) non-classic phenotype. The most frequent variants were c.292+5G>A in 26% (15/58) of patients and Del/Del in 21% (12/58) of them. Conclusions The most frequent mutation in our study population was the c.292+5G>A, which was found in 15/58 patients. This rare variant has only been reported in three other studies so far but as an infrequent mutation in CAH patients. The genetic characteristics of Costa Rican patients differ from what has been documented worldwide and could respond to a founder effect.

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Section: Discussionmentioning

confidence: 99%

CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica

Umaña-Calderón

Acuña-Navas

Alvarado

et al. 2021

Molecular Genetics and Metabolism Reports

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“…Children and adolescents with appropriately treated CAH exhibit normal cognitive and executive function ( Parker et al, 2006 ; Messina et al, 2020a ). However, parental reports indicate increased social problems on the Childhood Behavior Checklist ( Zanella et al, 2018 ; Messina et al, 2020b ). This may happen in 47,XXY as well, so we wondered how the potential mitigation of a supernumerary X with CAH could affect this aspect.…”

Section: Discussionmentioning

confidence: 99%

“… Parker et al (2006) reported a boy with positive newborn screening of CAH and later diagnosis of 48,XXXY/47, XXY mosaicism after concerning physical exam that included poor weight gain, microcephaly, and mild developmental delay. Another study reported a boy who was diagnosed with CAH at 2 years old but evaded evaluation for 47,XXY until he was 18 years old, primarily due to low testicular volume ( Zanella et al, 2018 ). We present a case of a young male with the salt-wasting phenotype of caused by 21OHD CAH and 47,XXY.…”

Section: Introductionmentioning

confidence: 99%

Case Report: Infant With Congenital Adrenal Hyperplasia and 47,XXY

Song¹,

Gropman

Benjamin

et al. 2022

Front. Genet.

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Congenital adrenal hyperplasia is a group of autosomal recessive disorders in which enzymes in the cortisol biosynthesis pathways are disrupted by gene mutations. The most common form of congenital adrenal hyperplasia, caused by 21-hydroxylase deficiency, is characterized by decreased cortisol and aldosterone synthesis and excessive androgen production. Adult height is often compromised in affected patients. Intellectual capability remains intact in patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency, based on previous studies. 47,XXY (KS) is a sex chromosomal aneuploidy that manifests with hypergonadotropic hypogonadism, tall stature, and variable intellectual and behavioral dysfunction. This clinical report describes an infant with 21-hydroxylase deficiency congenital adrenal hyperplasia and 47,XXY. The results of his neurodevelopmental, endocrine, neurological, and physical therapy evaluations during his first 22 months are included and were normal. This is the first published case investigating the neurodevelopmental profile of a patient with the combination of these two genetic disorders.

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“…So, we can speculate that high adrenal androgen secretion by CAH had a greater relevance than the low testicular androgen production, typical of KS. Till now there are 5 reported cases of co-occurrence of KS with CAH, one of them had 3BHSD2 deficiency but with a different presentation and the rest of them had 21-OH deficiency ( 23 , 24 , 25 , 26 , 27 ). Four of them were detected in boys and another one in a 51-year-old male.…”

Section: Discussionmentioning

confidence: 99%

A rare variety of congenital adrenal hyperplasia with mosaic Klinefelter syndrome: a unique combination presenting with ambiguous genitalia and sexual precocity

Shehab

Mahmood

Hasanat

et al. 2018

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryCongenital adrenal hyperplasia (CAH) due to the three-beta-hydroxysteroid-dehydrogenase (3β-HSD) enzyme deficiency is a rare autosomal recessive disorder presenting with sexual precocity in a phenotypic male. Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy presenting with hypergonadotropic hypogonadism in a male. However, only a handful of cases of mosaic KS have been described in the literature. The co-existence of mosaic KS with CAH due to 3β-HSD enzyme deficiency portrays a unique diagnostic paradox where features of gonadal androgen deficiency are masked by simultaneous adrenal androgen excess. Here, we report a 7-year-old phenotypic male boy who, at birth presented with ambiguous genitalia, probably a microphallus with penoscrotal hypospadias. Later on, he developed accelerated growth with advanced bone age, premature pubarche, phallic enlargement and hyperpigmentation. Biochemically, the patient was proven to have CAH due to 3β-HSD deficiency. However, the co-existence of bilateral cryptorchidism made us to consider the possibility of hypogonadism as well, and it was further explained by concurrent existence of mosaic KS (47,XXY/46,XX). He was started on glucocorticoid and mineralocorticoid replacement and underwent right-sided orchidopexy on a later date. He showed significant clinical and biochemical improvement on subsequent follow-up. However, the declining value of serum testosterone was accompanied by rising level of FSH thereby unmasking hypergonadotropic hypogonadism due to mosaic KS. In future, we are planning to place him on androgen replacement as well.Learning points:Ambiguous genitalia with subsequent development of sexual precocity in a phenotypic male points towards some unusual varieties of CAH.High level of serum testosterone, adrenal androgen, plasma ACTH and low basal cortisol are proof of CAH, whereas elevated level of 17-OH pregnenolone is biochemical marker of 3β-HSD enzyme deficiency.Final diagnosis can be obtained with sequencing of HSD3B2 gene showing various mutations.Presence of bilateral cryptorchidism in such a patient may be due to underlying hypogonadism.Karyotyping in such patient may rarely show mosaic KS (47,XXY/46,XX) and there might be unmasking of hypergonadotropic hypogonadism resulting from adrenal androgen suppression from glucocorticoid treatment.

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A Klinefelter boy with congenital adrenal hyperplasia: too much or too little androgens?

Cited by 4 publications

References 10 publications

CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica

CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica

Case Report: Infant With Congenital Adrenal Hyperplasia and 47,XXY

A rare variety of congenital adrenal hyperplasia with mosaic Klinefelter syndrome: a unique combination presenting with ambiguous genitalia and sexual precocity

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