Klinefelter Syndrome in Childhood: Variability in Clinical and Molecular Findings

Abstract

Objective:Klinefelter syndrome (KS) is the most common (1/500–1/1000) chromosomal disorder in males, but only 10% of cases are identified in childhood. This study aimed to review the data of children with KS to assess the age and presenting symptoms for diagnosis, clinical and laboratory findings, together with the presence of comorbidities.Methods:Twenty-three KS patients were analyzed retrospectively. Age at admission, presenting symptoms, comorbid problems, height, weight, pubertal status, biochemical findings, hormone profiles, bone mineral density and karyotype were evaluated. Molecular analysis was also conducted in patients with ambiguous genitalia.Results:The median age of patients at presentation was 3.0 (0.04-16.3) years. Most of the cases were diagnosed prenatally (n=15, 65.2%). Other reasons for admission were scrotal hypospadias (n=3, 14.3%), undescended testis (n=2, 9.5%), short stature (n=1, 4.8%), isolated micropenis (n=1, 4.8%) and a speech disorder (n=1, 4.8%). The most frequent clinical findings were neurocognitive disorders, speech impairment, social and behavioral problems and undescended testes. All except two patients were prepubertal at admission. Most of the patients (n=20, 86.9%) showed the classic 47,XXY karyotype. Steroid 5 alpha-reductase 2 gene and androgen receptor gene mutations were detected in two of the three cases with genital ambiguity.Conclusion:Given the large number of underdiagnosed KS patients before adolescence, pediatricians need to be aware of the phenotypic variability of KS in childhood. Genetic analysis in KS patients may reveal mutations associated with other forms of disorders of sex development besides KS.

An Overview on Klinefelter’s: Clinical Features and Management in Pediatric Population

“…Other less common physical findings include hypertelorism and macroglossia. Later in early childhood, young boys may experience linguistic delay and speech impairment and, therefore, may suffer from learning difficulties and have both social and behavioral problems [7,8]. During puberty, Klinefelter syndrome is more readily diagnosed, as these individuals may have an incomplete pubertal development.…”

“…Another common finding is the eunuchoid skeleton where the upper to lower body ratio is skewed to the latter; despite the variability of the symptoms mentioned above and signs, an almost universal finding is firm and small testis with a volume of <4ml, which is the result of progressive fibrosis and destruction to testicular tissue. A small exception of such findings is patients with mosaic KS with normal-sized pairs of the testis [5,8,9]. An overwhelming majority of KS patients go unnoticed till they reach adulthood.…”

Klinefelter Syndrome: Clinical Spectrum Based on 44 Consecutive Cases from a South Indian Tertiary Care Center

“…Klinefelter variant karyotype was observed exclusively in children, and their presentation was predominantly non-gonadal issues like behavioral abnormalities, intellectual problems, and cardiac anomalies similar to previous observations. [14] Klinefelter variant karyotype 48 XXYY found in two of our cohorts is infrequently observed and is associated with more pronounced phenotype abnormalities and greater cognitive impairment. [15] The rarest variant, 49 XXXXY, observed in two patients occurs in 1:85,000 to 1:1,00,000 and is described to be the most severe variant.…”

Bone Mineral Density and Bone Markers in Juvenile Idiopathic Arthritis Patients

“…Osteoporosis can be diagnosed clinically in children. Osteoporosis is diagnosed in patients with a BMD Z-score of less than or equal to -2.0 and a clinically significant fracture [16] . For all JIA categories, the disease activity score (JADAS 27) had a cutoff score of 1, and the cutoff points for the classification of minimum disease activity for oligoarticular JIA and polyarticular JIA were 1:2 and 1:3.8, respectively.…”