Vol. 16 nº 1 - Jan/Feb/Mar de 2022
Original Article Pages 97 to 104

Educational status, testosterone replacement, and intelligence outcomes in Klinefelter syndrome
Escolaridade, reposição de testosterona e desfechos de inteligência na síndrome de Klinefelter

Authors: Luciane Simonetti1; Magnus Regios Dias da Silva1; Claudia Berlim de Mello2


Descriptors: Klinefelter Syndrome; Phenotype; Intelligence; Testosterone; Educational Status.
Síndrome de Klinefelter; Fenótipo; Inteligência; Testosterona; Escolaridade.

Most male hypergonadotropic hypogonadism associated with infertility can be attributed to a single genetic condition such as Klinefelter syndrome (KS). This disease‚?Ts wide phenotypic variability is frequently associated with mosaic 47,XXY lineages and testosterone replacement. Early diagnosis and treatment have been associated with better cognitive and intellectual outcomes, but the scope of this influence requires further investigation.
OBJECTIVE: This study aimed to investigate the intelligence profile of a cohort of patients with KS, considering the influence of educational level and clinical variables.
METHODS: Twenty-nine (9‚?"65 years) individuals were submitted to the measures of intelligence quotient (IQ) (Wechsler‚?Ts Scales) and adaptive behavior (Vineland-II). Linear regression analysis included the participants‚?T educational level and clinical variables (i.e., comorbidities and use of testosterone) as predictors and intellectual performance and adaptive behavior as outcomes.
RESULTS: Scores varied from intellectual deficiency to average ranges (82.5+15.8). There were significant differences between adult‚?Ts and children‚?Ts IQ and between verbal and nonverbal indexes. The level of education predicted both IQ and adaptive behavior. Testosterone replacement therapy and absence of seizures predicted only adaptive behavior.
CONCLUSIONS: The level of education and hormonal therapy can be selectively implicated in the intellectual variability in KS.

A maioria dos casos de hipogonadismo hipergonadotr√≥fico masculino associado √† infertilidade pode ser atribu√≠da a uma √ļnica condi√ß√£o gen√©tica ‚?" a s√≠ndrome de Klinefelter (KS). A ampla variabilidade fenot√≠pica dessa doen√ßa est√° frequentemente associada a linhagens de mosaico 47,XXY e tamb√©m √† reposi√ß√£o de testosterona. O diagn√≥stico e o tratamento precoces t√™m sido associados a melhores desfechos em termos de cogni√ß√£o e intelig√™ncia, mas o escopo dessa influ√™ncia requer maior investiga√ß√£o.
OBJETIVO: Este estudo investigou o perfil de inteligência de uma coorte de pacientes com KS, considerando a influência do nível educacional e das variáveis clínicas.
M√%TODOS: Vinte e nove indiv√≠duos (9‚?"65 anos) foram submetidos a medidas de quociente de intelig√™ncia (escalas Wechsler) e de comportamento adaptativo (escala Vineland-II). A an√°lise de regress√£o linear considerou o n√≠vel educacional dos participantes e vari√°veis cl√≠nicas (comorbidades, uso de testosterona) como preditores e desempenho intelectual e comportamento adaptativo como desfechos.
RESULTADOS: Os resultados mostraram escores que variaram de defici√™ncia intelectual √† faixa m√©dia (82,5+15,8). Houve diferen√ßas significativas entre os quocientes de intelig√™ncia de adultos e crian√ßas e entre os √≠ndices verbais e n√£o verbais. O n√≠vel educacional influenciou tanto o quociente de intelig√™ncia quanto o comportamento adaptativo. A terapia de reposi√ß√£o de testosterona e a aus√™ncia de convuls√Ķes influenciaram apenas o comportamento adaptativo. .
CONCLUS√ES: Sendo assim, n√≠vel educacional e terapia hormonal podem estar seletivamente implicados na variabilidade intelectual na KS.


Klinefelter syndrome (KS) is a male X-chromosome aneuploidy, resulting in 47,XXY karyotype1,2. It is the most frequent cause of hypergonadotropic hypogonadism and the main genetic cause of male infertility3,4, and it occurs in approximately 1 in 650 males5. The diagnosis usually occurs in adulthood due to infertility, when karyotyping test confirms X-chromosome polysomy 47,XXY, 48,XXXY, and 49,XXXXY or its mosaic forms 47,XXY/46,XY and 47,XXY/48,XXXY. The most well-known characteristics, alongside infertility, are gynecomastia, tall height, smaller testes and penis, azoospermia, and low levels of testosterone6,7.

Genotypic and phenotypic variability in KS is the subject of many studies8,9. Mosaicism and hormonal dysfunctions are related to a wide range of phenotypic manifestations10. In addition to infertility, individuals may present late-onset disorders, such as diabetes mellitus, obesity, metabolic and cardiovascular abnormalities, and epilepsy7,11. Cognitive, social, and language deficits have also been reported, but the overall intelligence quotient (IQ) is usually at average levels12-14. There is an increased risk for learning disabilities, poor adaptive functioning, internalizing symptoms (i.e., anxiety and depression), and attention-deficit hyperactivity disorder14. Impairments in executive functions, such as working memory and cognitive flexibility, may be present independently of neurodevelopmental disorders, probably due to the effects of hormonal dysfunctions on brain maturation15,16. The phenotypic heterogeneity in KS incurs diagnosis and treatment delays. There is evidence that early hormonal therapy minimizes cardiovascular and metabolic dysfunctions11 and has positive effects on cognitive and behavioral functioning17,18.

Since delayed treatment and higher morbidity in KS have been associated with low socioeconomic status3,19, analysis of influences of clinical and educational variables may favor a better understanding of intellectual variability. This study aimed to investigate the IQ and adaptive behavior of a sample of Brazilian individuals with KS, considering the association of educational and clinical variables. We hypothesized that higher educational levels and testosterone replacement would be associated with better outcomes. Therefore, this study is of special relevance since results may contribute to both the understanding of phenotypic characteristics of KS and the clinical follow-up of diagnosed individuals.


Participants and study design

This study followed a cross-sectional design for clinical studies, with a report on series of patients with an outcome of interest. A total of 29 individuals with KS (28 with 47,XXY karyotype and 1 with 48,XXXY karyotype) aged from 9 to 65 years were enrolled in the study. All were recruited from the Development Ambulatory of the Endocrinology Division of the Medical School of the Universidade Federal de S√£o Paulo, Brazil. A clinical endocrinologist examined all participants. The diagnosis was based on a thorough investigation, involving physical examination, assessment of hormone levels, and karyotyping. Data regarding hormone levels were obtained from medical records. Testosterone levels were measured by using liquid chromatography-tandem mass spectrometry in the same laboratory.

Information concerning clinical and socioenvironmental characteristics of participants was obtained by means of interviews with the adult participants or with the children‚?Ts and adolescents‚?T caregivers. Clinical variables included the history of delay in language development, seizures, mood oscillations, and testosterone replacement. Language delays have been associated with long-term consequences for typically developing children and are present in most neurodevelopmental disorders20. Socioenvironmental variables included age and educational level of participants or of their caregivers. We considered educational level as years spent at school.

This study was in accordance with all ethical norms and approved by the Research Ethics Committee of Universidade Federal de S√£o Paulo (1180/2016). All adult subjects signed a consent form, as well as the legal guardians of those under the age of 18. All children and adolescents also signed the assent forms. All assessment procedures were executed from April 2017 to December 2018.

Intellectual assessment procedures

Intellectual assessment focused on IQ and adaptive behavior. IQ was assessed with the Brazilian versions of the Wechsler Adult Intelligence Scale (WAIS-III)21 and the Wechsler Intelligence Scale for Children (WISC-IV)22. The Vineland-II Adaptive Behavior Scale (VABS-II) was used for both age groups23. Assessment occurred individually in two sessions of 90-min each.

The WAIS-III comprises 13 core subtests and the WISC-IV comprises 10 subtests. Since some of the subtests differ in versions, we included the supplementary Picture Completion, Arithmetic and Information from the WISC-IV and Picture Arrangement from the WISC-III24 to assure equivalent measures for all age groups. The verbal indexes, such as Verbal Intelligence Quotient (VIQ; WAIS-III) and Verbal Comprehension Index (VCI; WISC-IV), and the nonverbal indexes, such as Performance IQ (PIQ; WAIS-III) and Perceptual Reasoning Index (PRI; WISC-IV), were compared. The VABS-II covers four domains, namely, communication, daily living skills, socialization, and motor skills. The overall scores of both scales are expressed as standard scores (mean=100, standard deviation [SD]=15).

Statistical analysis

Descriptive analysis was used for sociodemographic and clinical characteristics. To investigate the associations among educational, clinical, and intellectual variables, simple and exploratory linear regression models were used. The adequacy of models was evaluated by the normality of residues observed in qqplot graphs. RStudio© and GraphPad Prism© software were used for the analysis. The level of significance was set to be 0.05%.


Educational and clinical data are presented in Table 1. The sample is composed of 6 children and adolescents aged 9‚?"17 years (Mage=13.17, SD=3.4), and 23 adults aged from 18 to 65 years (Mage=35.3, SD=14.1). The average education level of participants and their caretakers was 6.9 (SD=4.5) years and 5.9 (SD=4.3) years, respectively. Most had attended or were still attending public schools; 34.5% were illiterate. Mood oscillations were reported in 79% of cases and history of language delay in 45%. A proportion of 62% was on testosterone replacement treatment.

Intellectual performance data are presented in Table 2.

IQ varied from intellectual disability to average levels. Important differences (26.7 points) between the mean IQ obtained by children/adolescents and adults (see Table 2) were detected. For both age ranges, a better performance was detected in nonverbal indices (PIQ: M=92.6, SD=16.7 and PRI: M=71.7, SD=18.8). Children/adolescents showed intellectual disability and a significant discrepancy (20.7 points) between verbal and nonverbal indices. Of 13 participants with IQs in intellectual disability or borderline levels, 7 presented neurological (e.g., epilepsy and episodic ataxia), psychiatric (e.g., schizophrenia and autism), skeletal, or cardiac dysfunctions.

The highest scores were observed in Digit Symbol subtest, which requires visuomotor coordination and processing speed, and the lowest in Vocabulary and Comprehension, which assesses concept formation and understanding of social situations. The overall mean score for adaptive behaviors was moderately below normative parameters (72.3; SD=23.6). Lower scores were observed in the Communication (i.e., receptive, expressive, and written) and Motor domains.

Linear regression analysis revealed higher IQ (B=22.67, p<0.001) and adaptive index (B=18.67, p=0.012) in participants with more than 10 years of education when compared with those up to 5 years. The mother‚?Ts education level showed no effect for both measures. Full IQ was higher among participants with no history of seizures (B=-14.19, p=0.048) and under hormone replacement treatment (B=12.22, p=0.041) (Tables 3 and 4).

A Pearson correlation analyzed the associations between testosterone levels and intellectual scores in 28 participants because of missing data in medical records (Figure 1). All datasets followed the Gaussian distribution by using Kolmogorov-Smirnov test. Statistical significance was found for VIQ.

Figure 1. Graphic representation of simple linear regression and correlation between total testosterone and intellectual performance (28 participants). Full-Scale (FSIQ), Verbal (VIQ), and Performance (PIQ) Intelligence Quotient in Klinefelter syndrome cohort. Gray shaded area represents the reference range for
total testosterone measured by liquid chromatography tandem mass spectrometry (241‚?"827 ng/dL). Pearson‚?Ts correlation r=0.4016, p=0.0341 for VIQ.
FSIQ: Full-Scale; VIQ: Verbal Intelligence Quotient; PIQ: Performance Intelligence Quotient.


This study provides information concerning intellectual variability in KS, which can contribute to clinical management as well as to further research purposes regarding phenotypic characteristics. As expected, having more years of schooling and being on testosterone replacement therapy predicted outcomes in our cohort of 29 patients with different ages. Moreover, clinical variables influenced only adaptive behavior. To the best of our knowledge, this was the first study to assess intelligence outcomes in KS, considering IQ and adaptive behavior measures, as well as environmental and clinical variable influences.

A total of 13 participants presented IQ in intellectual disability or borderline levels, including 4 participants aged <16 years. Reports of intellectual deficits in KS are not usual, regardless of age. For instance, in a sample of 47 patients diagnosed with extra X-chromosome and age ranging from 6 to 20 years, the IQs were in average levels13.

The lower IQ scores among our children/adolescents could be explained by the sample characteristics, since there were only four participants aged <16 years, but diagnostic conditions shall also be considered. Since KS is identified mainly in adulthood due to infertility, diagnosis in early ages is uncommon. Most of the prepubertal children treated in our endocrinology service were referred by pediatricians because of complaints of neurodevelopment delays, learning disabilities, or clinical conditions such as epilepsy and psychiatric disorders. In this study, all children and adolescents presented one or more of these clinical conditions, which can affect intellectual development. Four adult patients also reported clinical conditions, specifically seizures. Two of them were on anticonvulsant medication. The incidence of seizures in KS is estimated to be 5%2,25 and has been associated with mortality1 and low IQ25.

Verbal indexes were lower than nonverbal, in accordance with previous findings12,26-28, although the difference is not always statistically significant29-31. Worse performances in neuropsychological tasks that demand verbal processing in comparison with nonverbal have been frequently reported32,33. Interestingly, Vocabulary and Comprehension subtests‚?T scores were the lowest in our KS cohort, regardless of age. A qualitative analysis of participant‚?Ts answers indicates a poor understanding of social situations, shortcomings in practical reasoning, restricted vocabulary, and a concrete narrative. Low performance in Comprehension was reported previously12. The low scores seem to reflect everyday life problems that KS individuals struggle with. The low adaptive scores express the reduced levels of functionality and autonomy. Weaknesses in practical intelligence and poor understanding of social situations are possibly related to social cognition deficits usually reported in patients34,35.

Our results also indicate that intelligence variation was better explained by individual‚?Ts educational status rather than their caregivers‚?T. The influence of environmental factors on the expression of intelligence skills is well known. In typical development, verbal IQ variation is moderated by parental education36. In genetic conditions, this influence is a matter of controversy. For example, in a large cohort (n=1,909) of sibling pairs of adolescents with Fragile X syndrome, inheritability influenced more verbal IQ variation than environmental factors among participants with high-educated parents37. Significantly combined influences were observed only among those with parents with <12 years of education. In a study comparing 8- to 18-year-old American and Dutch KS boys, significantly higher VIQ and PIQ were found in the former32. Parental education, time of diagnosis (prenatal/postnatal), and testosterone replacement were associated with differences, indicating the impact of socioeconomic factors in accessing medical treatment.

This study has limitations since all participants were recruited from a single outpatient clinic where usually more symptomatic patients are addressed. However, it innovates by emphasizing clinical and educational influences on neurocognitive phenotype, this way providing useful information for multidisciplinary approaches. The earlier signs of immature adaptive behavior or learning disabilities among children and adolescents with 47,XXY are identified, the sooner they may be submitted to interventions for improving academic and social skills. Results may contribute for a better understanding of phenotypic variability in KS.

Our results indicate that educational level and clinical variables, such as testosterone replacement and history of seizures, can be implicated in intellectual heterogeneity in KS. Higher education levels seem to influence adaptive behavior development. Further studies may elucidate the impact of testosterone replacement on cognition and behavior in life span.


The authors thank the Instituto Jo Clemente for the support given in patients‚?T recruitment.

Authors‚?T contributions. LS: conceptualization, formal analysis, investigation, methodology, project administration, writing ‚?" original draft & writing ‚?" review and editing. CBM: conceptualization, investigation, project administration, supervision, validation, writing ‚?" original draft & writing ‚?" review and editing. MRDS: conceptualization, formal analysis, funding acquisition, investigation, methodology, supervision & validation.


1. Swerdlow AJ, Higgins CD, Schoemaker MJ, Wright AF, Jacobs PA. Mortality in patients with Klinefelter syndrome in Britain: a cohort study. J Clin Endocrinol Metab. 2005;90(12):6516-22. https://doi.org/10.1210/jc.2005-1077

2. Bojesen A, Kristensen K, Birkebaek NH, Fedder J, Mosejilde L, Bennett P, et¬†al. The metabolic syndrome is frequent in Klinefelter‚?Ts syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care. 2006;29(7):1591-8. https://doi.org/10.2337/dc06-0145

3. Bojesen A, Juul S, Birkebaek NH, Gravholt CH. Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses. J Clin Endocrinol Metab. 2006;91(4):1254-60. https://doi.org/10.1210/jc.2005-0697

4. Richard-Eaglin A. Male and female hypogonadism. Nurs Clin North Am. 2018;53(3):395-405. https://doi.org/10.1016/j.cnur.2018.04.006

5. Kanakis GA, Nieschlag E. Klinefelter syndrome: more than hypogonadism. Metabolism. 2018;86:135-44. https://doi.org/10.1016/j.metabol.2017.09.017

6. Groth KA, Skakkebaek A, Host C, Gravholt CH, Bojesen A. Clinical review: Klinefelter syndrome - a clinical update. J Clin Endocrinol Metab. 2013;98(1):20-30. https://doi.org/10.1210/jc.2012-2382

7. Chang S, Skakkebaek A, Trolle C, Bojesen A, Hertz JM, Cohen A, et al. Anthropometry in Klinefelter syndrome - multifactorial influences due to CAG length, testosterone treatment and possibly intrauterine hypogonadism. J Clin Endocrinol Metab. 2015;100(3):E508-17. https://doi.org/10.1210/jc.2014-2834

8. Gravholt CH, Chang S, Wallentin M, Fedder J, Moore P, Skakkebaek A. Klinefelter syndrome: integrating genetics, neuropsychology, and endocrinology. Endocr Rev. 2018;39(4):389-423. https://doi.org/10.1210/er.2017-00212

9. Flannigan R, Patel P, Paduch DA. Klinefelter syndrome. The effects of early androgen therapy on competence and behavioral bhenotype. Sex Med Rev. 2018;6(4):595-606. https://doi.org/10.1016/j.sxmr.2018.02.008

10. Mohd Nor NC, Jalaludin MY. A rare 47XXY/46XX mosaicism with clinical features of Klinefelter syndrome. Int J Pediatr Endocrinol. 2016;2016:11. https://doi.org/10.1186/s13633-016-0029-3

11. Calogero AE, Giagulli VA, Mongioi LM, Triggiani V, Radicioni AF ,Jannini EA, et al. Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders. J Endocrinol Invest. 2017;40(7):705-12. https://doi.org/10.1007/s40618-017-0619-9

12. S√łrensen K. Physical and mental development of adolescent males with Klinefelter syndrome. Horm Res. 1992;37 Suppl 3:55-61. https://doi.org/10.1159/000182402

13. Rovet J, Netley C, Bailey J, Keenan M, Stewart D. Intelligence and achievement in children with extra X aneuploidy: a longitudinal perspective. Am J Med Genet. 1995;60(5):356-63. https://doi.org/10.1002/ajmg.1320600503

14. Tartaglia N, Cordeiro L, Howell S, Wilson R, Janusz J. The spectrum of the behavioral phenotype in boys and adolescents 47,XXY (Klinefelter syndrome). Pediatr Endocrinol Rev. 2010;80(1):151-59. PMID: 21217607

15. Skakkebæk A, Moore PJ, Pedersen AD, Bojesen A, Kristensen MK, Fedder J, et al. The role of genes, intelligence, personality, and social engagement in cognitive performance in Klinefelter syndrome. Brain Behav. 2017;7(3):e00645. https://doi.org/10.1002/brb3.645

16. Davison KK, Susman, EJ. Are hormone levels and cognitive ability related during early adolescence? Int J Behav Dev. 2001;25(5):416-28. https://doi.org/10.1080/016502501316934842

17. Samango-Sprouse CA, Sadeghin T, Mitchell FL, Dixon T, Stapleton E, Kingery M, et al. Positive effects of short course androgen therapy on the neurodevelopmental outcome in boys with 47,XXY syndrome at 36 and 72 months of age. Am J Med Genet A. 2013;161A(3):501-8. https://doi.org/10.1002/ajmg.a.35769

18. Samango-Sprouse C, Stapleton EJ, Lawson P, Mitchell F, Sadeghin T, Powell S, et al. Positive effects of early androgen therapy on the behavioral phenotype of boys with 47,XXY. Am J Med Genet C Semin Med Genet. 2015;169(2):150-7. https://doi.org/10.1002/ajmg.c.31437

19. Bojesen A, Stochholm K, Juul S, Gravholt CH. Socioeconomic trajectories affect mortality in Klinefelter syndrome. J Clin Endocrinol Metab. 2011;96(7):2098-104. https://doi.org/10.1210/jc.2011-0367

20. Levy A. ‚?~Developmental delay‚?T reconsidered: the critical role of age-dependent, co-variant development. Front Psychol. 2018;9:503. https://doi.org/10.3389/fpsyg.2018.00503

21. Nascimento E. Escala de Inteligência Wechsler para Adultos. 3rd ed. Manual; Adaptação e padronização de uma amostra brasileira. São Paulo: Casa do Psicólogo; 2004.

22. Rueda FJM, Noronha APP, Sisto FF, Santos AAA, Castro NR. WISC-IV. Escala Wechsler de Intelig√™ncia para Crian√ßas. Manual de Instru√ß√Ķes para Aplica√ß√£o e Corre√ß√£o. 4th ed. S√£o Paulo: Casa do Psic√≥logo; 2013.

23. Sparrow SS, Cicchetti DV, Balla DA. Vineland II: Vineland Adaptive Behavior Scales. 2nd ed. Minneapolis: Pearson Assessments; 2005.

24. Figueiredo VLM. WISC-III. Escala de inteligência Wechsler para crianças. Manual. São Paulo: Casa do Psicólogo; 2002.

25. Tatum WO 4th, Passaro EA, Elia M, Guerrini R, Gieron M, Genton P. Seizures in Klinefelter‚?Ts syndrome. Pediatr Neurol. 1998;19(4):275-8. https://doi.org/10.1016/s0887-8994(98)00055-1

26. Skakkebæk A, Gravholt CH, Rasmussen PM, Bojesen A, Jensen JS, Fedder J, et al. Neuroanatomical correlates of Klinefelter syndrome studied in relation to the neuropsychological profile. Neuroimage Clin. 2013;4:1-9. https://doi.org/10.1016/j.nicl.2013.10.013

27. Skakkebæk A, Wallentin M, Gravholt CH. Neuropsychology and socioeconomic aspects of Klinefelter syndrome: new developments. Curr Opin Endocrinol Diabetes Obes. 2015;22(3):209-16. https://doi.org/10.1097/MED.0000000000000157

28. Melogno S, Pinto MA, Orsolini M, Tarani L. Beyond the literal meaning of words in children with Klinefelter syndrome: two case studies. Brain Sci. 2018;8(9):171. https://doi.org/10.3390/brainsci8090171

29. Verri A, Carmen D, Anna C, Federica C, Anna M, Chiara C. Variability in cognitive behavioral phenotypes in Klinefelter syndrome (KS) and other sex chromosomal aneuploidies (SCAs). Andrology (Los Angeles). 2017;6(1):1-9. https://doi.org/10.4172/2167-0250.1000175

30. Lam√īnica DAC, Ribeiro CC, Baldin MS, Tabaquim MLM. S√≠ndrome de Klinefelter: avalia√ß√£o fonoaudiol√≥gica e neuropsicol√≥gica. Rev CEFAC. 2018;20(5):665-71. https://doi.org/10.1590/1982-021620182056818

31. Foland-Ross LC, Ross JL, Reiss AL. Androgen treatment effects on hippocampus structure in boys with Klinefelter syndrome. Psychoneuroendocrinology 2019;100:223-28. https://doi.org/10.1016/j.psyneuen.2018.09.039

32. Samango-Sprouse C, Stapleton E, Chea S, Lawson P, Sadeghin T, Cappello C, et al. International investigation of neurocognitive and behavioral phenotype in 47,XXY (Klinefelter syndrome): predicting individual differences. Am J Med Genet A. 2018;176(4):877-85. https://doi.org/10.1002/ajmg.a.38621

33. Lee NR, Wallace GL, Clasen LS, Lenroot RK, Blumenthal JD, White SL, et al. Executive function in young males with Klinefelter (XXY) syndrome with and without comorbid attention-deficit/hyperactivity disorder. J Int Neuropsychol Soc. 2011;17(3):522-30. https://doi.org/10.1017/S1355617711000312

34. van Rijn S, de Sonneville L, Swaab H. The nature of social cognitive deficits in children and adults with Klinefelter syndrome (47,XXY). Genes Brain Behav. 2018;17(6):e12465. https://doi.org/10.1111/gbb.1246

35. Morel A, Peyroux E, Leleu A, Favre E, Franck N, Demily C. Overview of social cognitive dysfunctions in rare developmental syndromes with psychiatric phenotype. Front Pediatr. 2018;6:102. https://doi.org/10.3389/fped.2018.00102

36. Glaser B, Hessl D, Dyer-Friedman J, Johnston C, Wisbeck J, et al. Biological and environmental contributions to adaptive behavior in fragile X syndrome. Am J Med Genet A. 2003;117A(1):21-9. https://doi.org/10.1002/ajmg.a.10549

37. Rowe DC, Jacobson KC, Van den Oord EJ. Genetic and environmental influences on vocabulary IQ: parental education level as moderator. Child Dev. 1999;70(5):1151-62. https://doi.org/10.1111/1467-8624.00084

This study was conducted by the Division of Endocrinology, Department of Medicine, Universidade Federal de S√£o Paulo, S√£o Paulo, SP, Brazil.

1. Universidade Federal de S√£o Paulo, Departamento de Medicina, Divis√£o de Endocrinologia, S√£o Paulo SP, Brazil
2. Universidade Federal de S√£o Paulo, Departamento de Psicobiologia, S√£o Paulo SP, Brazil


Claudia Berlim de Mello
Email: claudia.berlim@unifesp.br

Received on May 18, 2021
Received in its final form on September 27, 2021
Accepted on October 03, 2021

Disclosure: The authors report no conflicts of interest

Funding: This study was funded by Conselho Nacional de Desenvolvimento Cient√≠fico e Tecnol√≥gico ‚?" CNPq (Process 141624/2016-7) and S√£o Paulo Research Foundation ‚?" FAPESP (14/06570-6 and 18/03511-0)


Home Contact