Androgen Receptor CAG<sub>n</sub>Repeat Length Influences Phenotype of 47,XXY (Klinefelter) Syndrome

Zinn, Andrew R.; Ramos, Purita; Elder, F.F.B.; Kowal, Karen; Samango‐Sprouse, Carole; Ross, Judith L.

doi:10.1210/jc.2005-0432

Cited by 107 publications

(94 citation statements)

References 46 publications

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“…(Xm) (55.56%, 5) and paternally derived X (Xp) (44.44%, 4) agreed with that of the study by Harvey et al, [10] and Zinn et al, [13] (56% Xm; 44% Xp). The determined percentage of the parental origin of X in KFS, in the present study, could be interpreted that more or less the non-disjunction of X during gametogenesis might be in line with proportional distribution reported in the literature.…”

Section: Discussionsupporting

confidence: 89%

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Association of Parental Origin with Clinical Profile in Klinefelter Syndrome

Vallabhajosyula

Rajangam

2015

JCDR

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Section: Discussionsupporting

confidence: 89%

“…Large sample of KFS was investigated Jacobs [12] and Harvey et al, [10] used X centromeric probe. The reports from their metacentric study show Xm and Xp in 111 and 61 KFS male respectively CAG repeat length of AR gene was reported by Zinn et al, [13] and Stemkens et al, [14] with equal percentage Xm or Xp.…”

Section: Discussionmentioning

confidence: 69%

Association of Parental Origin with Clinical Profile in Klinefelter Syndrome

Vallabhajosyula

Rajangam

2015

JCDR

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“…Thus, a delayed initiation of testosterone treatment in the patients of our study could explain adult penile length. Another hypothesis could be a variable length of the CAG repeats in exon 1 of the androgen receptor gene, which can modify hormone responsiveness and influence penile length in Klinefelter syndrome (24) as well as in normal 46,XY males (25). One of the most relevant results of our study was the short final stature, with 62% of the patients measuring !160 cm (!K2 SDS), independent of IUGR, testosterone treatment, or GH treatment.…”

Section: Patient Gh Therapymentioning

confidence: 77%

Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys

Martinerie

Morel²,

Pienkowski³

et al. 2012

European Journal of Endocrinology

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Context: Gender assignment followed by surgery and hormonal therapy is a difficult decision in the management of 45,X/46,XY patients with abnormal external genitalia at birth considering the paucity of studies evaluating pubertal development and fertility outcome, most notably for patients raised as boys. Objective: The purpose of this study was to describe the pubertal course of 20 45,X/46,XY patients born with ambiguous genitalia and raised as boys. Methods: This is a multicenter retrospective study. Results: Mean age at study was 25.6G2.4 years. Eighty-five percent of the patients presented a 'classical' mixed gonadal dysgenetic phenotype at birth. Puberty was initially spontaneous in all but three boys, although in six other patients, testosterone therapy was subsequently necessary for completion of puberty. Sixty-seven percent of the remaining patients presented signs of declined testicular function at the end of puberty (increased levels of FSH and low levels of testosterone and/or inhibin B). Moreover, an abnormal structure of the Y chromosome, known to alter fertility, was found in 10 out of 16 (63%) patients. Two patients developed testicular cancer. Half of the patients have adult penile length of !80 mm. Mean adult height is 156.9G2 cm, regardless of GH treatment. Conclusions: In summary, 45,X/46,XY children born with ambiguous genitalia and raised as boys have an altered pubertal course and impaired fertility associated with adult short stature, which should, therefore, be taken into consideration for the management of these patients.

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“…The CAG-repeat length of the AR gene is associated with taller adult height and more gynecomastia in adult males [Zitzmann et al, 2004], and with shorter penile length in children with XXY [Zinn et al, 2005]. The longer CAG-repeat polymorphism codes for a receptor that is less responsive to androgen, thus perhaps low receptor responsiveness coupled with mild-moderate androgen deficiency contributes to the more severe phenotype in XXY.…”

Section: Discussionmentioning

confidence: 99%

A new look at XXYY syndrome: Medical and psychological features

Tartaglia

Davis

Hench

et al. 2008

American J of Med Genetics Pt A

141

210

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XXYY syndrome occurs in approximately 1:18,000-1:40,000 males. Although the physical phenotype is similar to 47,XXY (tall stature, hypergonadotropic hypogonadism, and infertility), XXYY is associated with additional medical problems and more significant neurodevelopmental and psychological features. We report on the results of a cross-sectional, multicenter study of 95 males age 1-55 with XXYY syndrome (mean age 14.9 years), describing diagnosis, physical features, medical problems, medications, and psychological features stratified by age groups. The mean age of diagnosis was 7.7 years. Developmental delays and behavioral problems were the most common primary indication for genetic testing (68.4%). Physical and facial features varied with age, although hypertelorism, clinodactyly, pes planus, and dental problems were common across all age groups. Tall stature was present in adolescents and adults, with a mean adult stature of 192.4 cm (SD 7.5; n = 22). Common medical problems included allergies and asthma (>50%), congenital heart defects (19.4%), radioulnar synostosis (17.2%), inguinal hernia and/or cryptorchidism (16.1%), and seizures (15%). Medical features in adulthood included hypogonadism (100%), DVT (18.2%), intention tremor (71%) and type II diabetes (18.2%). Brain MRI (n = 35) showed white matter abnormalities in 45.7% of patients and enlarged ventricles in 22.8%. Neurodevelopmental and psychological difficulties were a significant component of the behavioral phenotype, with developmental delays and learning disabilities universal but variable in severity. Twenty-six percent had full-scale IQs in the range of intellectual disability (MR), and adaptive functioning was significantly impacted with 68% with adaptive composite scores <70. Rates of neurodevelopmental disorders, including ADHD (72.2%), autism spectrum disorders (28.3%), mood disorders (46.8%), and tic disorders (18.9%), were elevated with 55.9% on psychopharmacologic medication overall. Recommendations for evaluation and treatment are summarized.

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Androgen Receptor CAG_nRepeat Length Influences Phenotype of 47,XXY (Klinefelter) Syndrome

Abstract: Normal genetic variation in the AR coding sequence may be clinically significant in the setting of early testicular failure and subnormal circulating testosterone levels, as occur in KS.

Cited by 107 publications

References 46 publications

Association of Parental Origin with Clinical Profile in Klinefelter Syndrome

Association of Parental Origin with Clinical Profile in Klinefelter Syndrome

Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys

A new look at XXYY syndrome: Medical and psychological features

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Androgen Receptor CAGnRepeat Length Influences Phenotype of 47,XXY (Klinefelter) Syndrome

Abstract: Normal genetic variation in the AR coding sequence may be clinically significant in the setting of early testicular failure and subnormal circulating testosterone levels, as occur in KS.

Cited by 107 publications

References 46 publications

Association of Parental Origin with Clinical Profile in Klinefelter Syndrome

Association of Parental Origin with Clinical Profile in Klinefelter Syndrome

Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys

A new look at XXYY syndrome: Medical and psychological features

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Product

Resources

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Androgen Receptor CAG_nRepeat Length Influences Phenotype of 47,XXY (Klinefelter) Syndrome