Table 1.

Characteristics of included studies.

Reference	n	Country	Setting	Study design	Methodology	Primary outcome	Measure	Comparator	JB quality score
Ferlin et al. (31)	62	Italy	Hospital clinic	Cross-sectional analysis/non-RCT	Interview, self-reported questionnaires	Type of sexual dysfunctions within KS	IIEF-15	60 aged-matched	6/8
Fisher et al. (32)	46	Italy	Hospital nits	Cross-sectional analysis	Clinical interviews, psychometric analysis	Prevalence of sexual disorders (GD, paraphilia) in KS	AQ, RME, GIDYQ-AA, SAST, SCL-90-R, IEEF,	43 male controls	7/8
Herlihy et al. (21)	87	Australia	Participant home	Cross-sectional analysis	DNA self-admin test, self-administered questionnaires	Psychosocial impact of KS on QoL	PWI, MBSRQ-AS, RSE, K10, short form-1, SIS	General population normative means	7/8
Sorensen (27)	14	Denmark	Schools and clinical setting	Cross-sectional analysis	Clinical examination/ psychological assessment	Physical and mental development in KS	WAIS, school attainment, behaviour rating schedules	19 male controls	6/8
Rapp et al. (23)	219	Germany	14 recruitment centres.	Cross-sectional analysis	Medical examination/interviews, (PRO) questionnaires	Measuring QoL in patients with (DSD)	WHOQOL-bref	Healthy European populations	8/8
van Rijn (35)	20	Netherlands	Not specified	Cross-sectional analysis	Self-reported questionnaires, salivary T	Effect of T levels on ‘social anxiety, social cognition’ in KS	FSIQ, KDEF, SCST, SAS	25 male controls	6/8
Skakkebaek et al. (33)	132	Denmark	University Hospital	Cross-sectional analysis	Questionnaires, salivary T	Determinants of anxiety and depression	WHOQOL-bref, SF-36, IIEF-15, demographics	313 matched controls	7/8
Skakkebaek et al. (34)	69	Denmark	Clinical	Cross-sectional analysis	Questionnaires, cognitive assessments	Cognitive performance in KS	NEO PI-R, AQ, FSIQ	69 matched controls	6/8
Van Rijn et al. (7)	34	Netherlands/Belgium	Academic medical clinics /support groups	Cross-sectional analysis	Patient- and parent-reported questionnaires	Social behavioural phenotype in children with KS	ADI-R, SRS, SAS, SSRS	46 male Controls	7/8
Van Rijn et al. (26)	31	Netherlands	Not Specified	Cross-sectional analysis	Self-administered questionnaires and tests	Social difficulties in adult men with Klinefelter syndrome	NART, WAIS-R IQ, SIB, Short form, AQ	2 male control groups (n = 20, n  = 24)	6/8
Liberato et al., (22)	58	Italy	Clinical	Cross-sectional analysis	Blood sampling, self-reported questionnaire, and clinical interview	Investigate fluid intelligence, personality traits, personality disorders (PD) in adult KS	SCIDII, MMPI2, SPM	Community samples	5/8
Nielsen & Pelsen (24)	34	Denmark	Clinical	Cohort longitudinal study	Telephone interview	Differences between KS and hypogonadal males with a normal karyotype 46, XY	Job status, Martial status and adoption, Criminality, illness ‘physical or mental’	16 hypogonadal males	6/11
Fabrazzo et al. (30)	23	Italy	Academic and medical clinics	Cross-sectional analysis	Questionnaires including pre-existing scales and interviews	Impact of 1 year on TRT on psychopathological recovery and QoL in KS	Q-LES-Q, SCL-90-R, MMSE, TCI-R.	23 matched healthy subjects.	7/8

AQ, Autism Spectrum Quotient (62); ADI-R, Autism diagnostic interview – Revised (73); GSIS, General symptomatic index score; GIDYQ-AA, Gender Identity/Dysphoria Questionnaires for Adults and Adolescents (63); IIEF, International Index of Erectile function (75); K10, Kessler Psychological Distress Scale (66); MMPI-2, Minnesota Multiphasic Personality Inventory 2 (70); MMSE, Minimental State Examination; MBSRQ-AS, Multidimensional body-self relations questionnaire (64); NEO PI-R, Revised NEO personality inventory (67); NART, National adult reading test (81); PWI, Personal Wellbeing index (42); QRI, Qualitative reading inventory (67); Q-LES-Q, Italian Quality of Life Enjoyment and Satisfaction Questionnaire (38); RSE, Rosenberg self-esteem test (65); SI, Social interaction; SAS, Social anxiety scale (78); SF1, short form 1 (61); SF-36, 36 Item short form survey (37); SPM, Standard Progressive Matrices (74); SRS, The Social Responsiveness Scale (80); SAST, Short Anxiety Screening test (76); SCID-II, Structured Clinical Interview for Axis II Disorders (71); SCST, Social cognitive skills test (77); SRSS, Social skills rating scale (79); SCL-90-R, Symptom Checklist-90-R; SLC-ANX/DEP, Subscales of Symptoms checklist 90 Anxiety/Depression (72); TCI-R, Temperament and Character Inventory-Revise; WHOQOL100, World Health Organisation Quality of Life 100 bref (14).