A Characteristic Cognitive and Behavioral Pattern as a Clue to Suspect Klinefelter Syndrome in Prepubertal Age

Maria Francesca Messina, MD; Domenica Lucia Sgrò, MD; Tommaso Aversa, MD; Maria Pecoraro, MD; Mariella Valenzise, MD; Filippo De Luca, MD


J Am Board Fam Med. 2012;25(5):745-749. 

In This Article

Abstract and Introduction


Klinefelter syndrome (KS) with the classic 47,XXY karyotype is the most frequent chromosomal aneuploidy, with a prevalence of 1 in 700 men; although the classic clinical picture is well-known and easily recognizable, most patients remain undiagnosed. The rate of diagnosis during childhood is extremely low, and only 10% of cases are identified before puberty, with a subsequent rate of ascertainment during lifetime of 25%. The low rate of timely diagnosis is because most of the classical signs and symptoms of androgen deficiency appear in mid- to late adolescence but it is important to recognize that adult men with KS may show a great variability in clinical and physical features. A common, often underappreciated, element in young boys and children with KS is the characteristic cognitive and behavioral pattern. We describe 2 patients who were diagnosed at 7.1 and 10 years through a characteristic neurocognitive profile. Both of them showed low-normal scores when evaluated by tests of general intelligence and a behavioral profile characterized by immaturity, low self-esteem, and learning disabilities. Clinical examination showed tall stature and progressive growth acceleration between 5 and 7 years, and one of them had hypoplastic scrotum with monolateral cryptorchidism. To achieve the goal of an early diagnosis of KS, it is necessary to increase medical awareness of the disease and, in particular, to augment pediatricians' knowledge that during prepubertal age pathognomonic clinical features of KS are often lacking but a characteristic cognitive and behavioral pattern is commonly present.


Klinefelter syndrome (KS) with the classic 47,XXY karyotype is the most frequent chromosomal aneuploidy, with a prevalence of 1 in 700 men,[1] and is the most common genetic form of male hypogonadism.[2] KS was first described in 1942 by Klinefelter et al[3] as a clinical entity characterized by gynecomastia, small testes, absent spermatogenesis, normal to moderately reduced Leydig cell function, and increased secretion of follicle-stimulating hormone (FSH). The classical phenotype of KS is well described in every textbook of medicine and is easily recognizable. Nonetheless, 70 years after its first description, this syndrome remains a largely undiagnosed condition.

The main reason for lack of diagnosis is that many affected patients present only discrete symptoms during their lifetime, and especially during childhood the clinical picture may be unimportant, with most of the signs and symptoms appearing only in mid to late adolescence. As a consequence, the rate of diagnosis during childhood is extremely low, with 10% of cases being identified before puberty;[4] if we consider that 10% are diagnosed prenatally and only 25% are recognized during their lifetime, we have to acknowledge that a huge percentage of KS patients remain undiagnosed. Here we describe the clinical presentation of 2 young boys who were diagnosed at a young age (ie, before 10 years). The correct diagnosis was suggested by a characteristic cognitive and behavioral pattern.