Neurocognitive development and capabilities in boys with 49,XXXXY syndrome

Abstract

49,XXXXY was previously associated with profound to severe intellectual deficits.However, prior research papers on the cognitive profiles of this population were confounded by small samples sizes, wide age spreads, and incomplete histories of testosterone replacement therapy. This study is the first comprehensive, international investigation of the neurocognitive aspects of 49,XXXXY, and the potential effects of biological treatment on this profile. Sixty-seven boys from infancy to 11 years of age were enrolled in this longitudinal study, with the majority of boys postnatally diagnosed though chromosomal analysis. These boys received a comprehensive neurocognitive evaluation tailored to specific language-based deficits and cognitive challenges. Results revealed higher neurocognitive capacities, both verbally and nonverbally, than previously reported in this disorder. Infant boys with 49,XXXXY who received early hormonal therapy (EHT) had significantly higher scores on the cognitive domain of the Bayley Scales of Infant Development than untreated infants (p = .013). In addition, treated school-aged participants had significantly better scaled scores than untreated boys in form completion (p = .042), a task that requires deductive reasoning, on nonverbal testing on the Leiter International Performance Scales.This study indicates greater cognitive capacities with a wide range of abilities in the child with 49,XXXXY, thus warranting further investigation to identify and understand the critical influences on the etiology and the variability of those capacities.49,XXXXY, sex chromosome aneuploidies, variant of 47,XXY (Klinefelter syndrome), X and Y chromosomal variation | INTRODUCTION49,XXXXY is the rarest X and Y chromosomal variation, with an estimated incidence of 1 in 85,000 to 1 in 100,000 live male births.

Report of a New Case of Pentasomy X Revealed by Status Epilepticus

“…The incidence of pentasomy X is unknown due to the extreme rarity of this aneuploidy. It is much rarer than the 49, XXXXY whose incidence in men is estimated by some authors at 1/85,000 [3,4]. To our knowledge, since 1983, only about 30 isolated cases of X pentasomy have been reported in the literature.…”

Clinical, Cognitive and Neurodevelopmental Profile in Tetrasomies and Pentasomies: A Systematic Review

“…In the same article, persistent sleep problems, particularly concerning sleep maintenance throughout the night, were described [ 15 ]. Recent research by Gropman et al [ 17 ] and colleagues better defined the presence of pervasive anxiety symptoms in 49, XXXXY patients.…”

“…Patients with high grade aneuploidies that underwent an early treatment with testosterone show persistent suppression of testicular secretory function [ 53 ]. In 2020, Gropman et al [ 17 ], demonstrated that affected patients treated with HRT obtained higher scores on the Bayley Scales of Infant Development (BSID-III), compared with untreated patients. In the same study, testosterone treatment appeared to have beneficial effects on both verbal and non-verbal domains, throughout infancy, preschool, and early childhood [ 17 ].…”

“…In 2020, Gropman et al [ 17 ], demonstrated that affected patients treated with HRT obtained higher scores on the Bayley Scales of Infant Development (BSID-III), compared with untreated patients. In the same study, testosterone treatment appeared to have beneficial effects on both verbal and non-verbal domains, throughout infancy, preschool, and early childhood [ 17 ]. In 2011, Samango-Sprouse [ 1 ] subjected 22 patients to multidisciplinary assessment (neurologic, neurocognitive, speech and language, endocrinologic), after dividing them into two equal groups: a treated (for three months) and untreated group.…”

Introduction: Comprehensive investigation into an international cohort of boys with 49,XXXXY

“…In addition, Porter et al (2020) explored the neurocognitive functioning of the 49,XXXXY population. This article demonstrates that boys with 49,XXXXY are more cognitively capable than previously appreciated and simultaneously recognizes the profound influence of complex language‐based learning dysfunction on neurocognitive performance.…”