Do the 48, XXYY males have a characteristic phenotype? A Review

Abstract

Data on fifty‐three patients with 48, XXYY chromosome complement were collected from the literature and personal correspondence and reviewed with the objective of delineating a ‘uniform phenotype.’ Although no single stigma was found to be characteristic of the 48, XXYY males, tall stature, low upper segment/lower segment ratio, mental retardation, and behavior problems in a phenotypic male (including prepubertal age group) should raise the question of a 48, XXYY chromosome basic defect. In the majority of cases testicular biopsies revealed varying degrees of atrophy, levels of FSH were elevated, and 17 KS were low to normal, both characteristics being comparable to those found in 47, XXY males. Dermatoglyphic changes were found to be reduced total finger ridge count, increased frequency of arches on fingers, presence of a hypothenar pattern, distally placed triradius, and occasional qimian crease.

A new look at XXYY syndrome: Medical and psychological features

“…This difference is due to the greater severity of developmental delays, dysmorphisms, medical problems, and neurodevelopmental disorders in children with XXYY compared to XXY leading to genetic testing. It is also an interesting contrast to the 11.3% of individuals with XXYY syndrome diagnosed prior to age 10 described in the last major case series published in 1970 [Borgaonkar et al, 1970], most likely due to the increased practice of genetic testing in children with developmental delays and neurodevelopmental disorders over the past 35 years.…”

“…Approximately 100 cases have been reported to date, often characterizing XXYY syndrome as a variant of 47,XXY Klinefelter syndrome due to a shared physical and endocrinologic phenotype including tall stature, microorchidism, hypergonadotropic hypogonadism, and infertility [Borgaonkar et al, 1970]. Although original reports suggested that there were no phenotypic differences from 47,XXY males [Townes et al, 1965], it is now recognized that 48,XXYY differs in its medical, neurodevelopmental, and behavioral characteristics [Parker et al, 1970;Zack, 1980;Grammatico et al, 1990;Linden et al, 1995;Zelante et al, 2003;Tartaglia et al, 2005].…”

“…The last large review of the XXYY syndrome phenotype summarizing the first 53 described cases was published by Borgaonkar et al [1970], with many subsequent individual case reports or short case series describing various medical and psychological features. In addition to the characteristic physical features of Klinefelter syndrome (tall stature, hypogonadism, gynecomastia), literature reports have described hypertelorism, cubitus varus, pes planus, clubfoot, clinodactyly, and scoliosis [Carr et al, 1961;Barr et al, 1964;Alter et al, 1966;Borgaonkar et al, 1970;Demirhan, 2003].…”

“…In addition to the characteristic physical features of Klinefelter syndrome (tall stature, hypogonadism, gynecomastia), literature reports have described hypertelorism, cubitus varus, pes planus, clubfoot, clinodactyly, and scoliosis [Carr et al, 1961;Barr et al, 1964;Alter et al, 1966;Borgaonkar et al, 1970;Demirhan, 2003]. Neurological problems, including seizures, intention tremor, hypotonia, and tics have also been reported in multiple patients [Robinson et al, 1964;Alter et al, 1966;Sorensen et al, 1978;Garry, 1980;Vanyan, 1984;Donati et al, 1992;Izumi and Tsubahara, 2000;Zelante et al, 2003], along with occasional structural brain abnormalities including agenesis of the corpus callosum [Nyberg et al, 1994] and frontoparietal cortical atrophy [Demirhan, 2003].…”

“…In older children and adults, full-scale IQ reports have ranged from as low as 35 up to 111 [Laurence et al, 1963;Sachsse et al, 1967], although in most cases IQ has ranged from 70 to 80 [Borgaonkar et al, 1970]. IQ profiles generally show a verbal IQ significantly lower than performance IQ [Zack, 1980], similar to the cognitive profile seen in 47,XXY males [Netley, 1986].…”