Clinical variability and novel neurodevelopmental findings in 49, XXXXY syndrome

Abstract

49, XXXXY is a rare chromosomal syndrome due to double nondisjunction of the replicating X chromosome. Considered a severe variant of XXY or Klinefelter syndrome, boys with this chromosome constitution are assumed to have severe mental retardation (MR) in addition to craniofacial, genital, endocrine, and heart abnormalities. Here, we present a multidisciplinary analysis including the clinical and neurobehavioral aspects of this condition in 20 boys with 49, XXXXY who share a common phenotype and neurobehavioral profile. The phenotypic presentation of the boys with 49, XXXXY shares some characteristics with 47, XXY, but there are also other unique and distinctive features. Previously unappreciated intact nonverbal skills are evident in conjunction with moderate to severe developmental dyspraxia. Variability in clinical and cognitive functioning may reflect skewed X inactivation, mosaicism, or other factors that warrant further investigation.

Frontal Aslant Tract Abnormality on Diffusion Tensor Imaging in an Aphasic Patient With 49, XXXXY Syndrome

“…In fact, the majority of children with 49, XXXXY have relatively intact nonverbal and also receptive vocabulary and comprehension skills 5 . Neurological examination and neuropsychological testing in our patient was consistent with this neurocognitive profile.…”

Musculoskeletal anomalies in a large cohort of boys with 49, XXXXY

“…Orthopedic abnormalities affect activities of daily living, mobility, neurodevelopmental progression, and ultimately, quality of life. In an effort to aid clinicians and families with the early identification of musculoskeletal anomalies, this article sought to survey the common musculoskeletal anomalies in this population and to expand data on birth weight, birth height, etc., that have been previously presented by Gropman et al [2010].…”

“…At birth, subtle facial dysmorphism may be noted, such as epicanthal folds, upslanting palpebral fissures, or full upper eyelids [Simpson et al, 2003;Visootsak, 2007;Gropman et al, 2010;Samango-Sprouse et al, 2011;Tartaglia et al, 2011]. Associated orthopedic abnormalities include congenital hip dysplasia, torticollis, radioulnar synostosis, congenital talipes equinovarus (club foot), and clinodactyly [Barr et al, 1962;Okuyama, 1993;Linden et al, 1995;Cammarata et al, 1999].…”

Chromosomal Variants in Klinefelter Syndrome

“…However, recent studies have reported that cognitive delays were not as significant as described in the past and personalities and learning styles are similar to 47,XXY cases [SamangoSprouse, 2001;Visootsak et al, 2001Visootsak et al, , 2007Visootsak and Graham, 2006;Gropman et al, 2010]. Variability in clinical and cognitive functioning may reflect skewed X inactivation, mosaicism, or other factors that warrant further investigation [Gropman et al, 2010]. Recently, Ottesen et al [2010] reported a study about the increased height in patients with additional sex chromosomes.…”