Brain imaging in neurogenetic conditions: Realizing the potential of behavioral neurogenetics research

Abstract

Behavioral neurogenetics research is a new method of scientific inquiry that focuses on investigation of neurodevelopmental dysfunction associated with specific genetic conditions. This research method provides a powerful tool for scientific inquiry into human gene-brain-behavior linkages that complements more traditional research approaches. In particular, the use of specific genetic conditions as models of common behavioral and cognitive disorders occurring in the general population can reveal insights into neurodevelopmental pathways that might otherwise be obscured or diluted when investigating more heterogeneous, behaviorally defined subject groups. In this paper, we review five genetic conditions that commonly give rise to identifiable neurodevelopmental and neuropsychiatric disability in children: fragile X syndrome, velo-cardio-facial syndrome, Williams syndrome, Turner syndrome, and Klinefelter syndrome. While emphasis is placed on describing the brain morphology associated with these conditions as revealed by neuroimaging studies, we also include information pertaining to molecular genetic, postmortem, and neurobehavioral investigations to illustrate how behavioral neurogenetics research can contribute to an improved understanding of brain disorders in childhood.

Fragile X syndrome: A review of clinical management

“…The inverse relationship of height and limb length with FMRP deficit supports a possible role of hypothalamic dysfunction in growth disturbances in FXS that may be more severe in those with the PWP (33). This dysfunction may cause a premature increase in the pulsating secretion of high doses of estrogen, thus leading to earlier epiphyseal maturation (34). The hypothesis of premature activation of the hypothalamic-pituitary-gonadal axis may explain the cause of growth impairment in FXS and occasional precocious puberty in females with FXS, a few cases have been reported (35,36).…”

Fragile X syndrome: A review of clinical management

“…The inverse relationship of height and limb length with FMRP deficit supports a possible role of hypothalamic dysfunction in growth disturbances in FXS that may be more severe in those with the PWP (33). This dysfunction may cause a premature increase in the pulsating secretion of high doses of estrogen, thus leading to earlier epiphyseal maturation (34). The hypothesis of premature activation of the hypothalamic-pituitary-gonadal axis may explain the cause of growth impairment in FXS and occasional precocious puberty in females with FXS, a few cases have been reported (35,36).…”

Early symptoms of autism spectrum disorder (ASD) in 1–8 year old children with sex chromosome trisomies (XXX, XXY, XYY), and the predictive value of joint attention

“…The current study aims to investigate the prospective impact of Sex Chromosome Trisomies (SCTs; XXX, XXY, XYY) on the appearance of early symptoms of Autism Spectrum Disorder (ASD), in children aged 1–8 years, with specific emphasis on the predictive value of Joint Attention on these ASD symptoms. The biological predisposition of SCTs allows us to study early social developmental pathways of a homogeneous group of children, and may be considered an ‘at risk’ group when it comes to neurobehavioral social adaptive development and related psychopathology [ 8 , 17 ], since the risk for ASD in this group has been found to be about 15–30% in children and adolescents [ 8 ]. The results of our study add to the understanding of the early prospective contribution of the extra X or Y chromosome on clinical risk for behavioral defined neurodevelopmental disorder such as ASD, and of early Joint Attention mechanisms predicting these ASD symptoms.…”

Renewal of the Neurophysiology of Language: Functional Neuroimaging

“…From a physiological standpoint, functional neuroimaging could prove a powerful tool for acquiring scientific insight into gene-brain-behavior links, which would provide an invaluable complement to more traditional research based on purely anatomical approaches to brain structures (326).…”

Fragile X syndrome: A review of clinical management

“…The inverse relationship of height and limb length with FMRP deficit supports a possible role of hypothalamic dysfunction in growth disturbances in FXS that may be more severe in those with the PWP (33). This dysfunction may cause a premature increase in the pulsating secretion of high doses of estrogen, thus leading to earlier epiphyseal maturation (34). The hypothesis of premature activation of the hypothalamic-pituitary-gonadal axis may explain the cause of growth impairment in FXS and occasional precocious puberty in females with FXS, a few cases have been reported (35,36).…”

Early symptoms of autism spectrum disorder (ASD) in 1–8 year old children with sex chromosome trisomies (XXX, XXY, XYY), and the predictive value of joint attention

“…The current study aims to investigate the prospective impact of Sex Chromosome Trisomies (SCTs; XXX, XXY, XYY) on the appearance of early symptoms of Autism Spectrum Disorder (ASD), in children aged 1–8 years, with specific emphasis on the predictive value of Joint Attention on these ASD symptoms. The biological predisposition of SCTs allows us to study early social developmental pathways of a homogeneous group of children, and may be considered an ‘at risk’ group when it comes to neurobehavioral social adaptive development and related psychopathology [ 8 , 17 ], since the risk for ASD in this group has been found to be about 15–30% in children and adolescents [ 8 ]. The results of our study add to the understanding of the early prospective contribution of the extra X or Y chromosome on clinical risk for behavioral defined neurodevelopmental disorder such as ASD, and of early Joint Attention mechanisms predicting these ASD symptoms.…”

Renewal of the Neurophysiology of Language: Functional Neuroimaging

“…From a physiological standpoint, functional neuroimaging could prove a powerful tool for acquiring scientific insight into gene-brain-behavior links, which would provide an invaluable complement to more traditional research based on purely anatomical approaches to brain structures (326).…”

Fragile X syndrome: A review of clinical management

“…The inverse relationship of height and limb length with FMRP deficit supports a possible role of hypothalamic dysfunction in growth disturbances in FXS that may be more severe in those with the PWP (33). This dysfunction may cause a premature increase in the pulsating secretion of high doses of estrogen, thus leading to earlier epiphyseal maturation (34). The hypothesis of premature activation of the hypothalamic-pituitary-gonadal axis may explain the cause of growth impairment in FXS and occasional precocious puberty in females with FXS, a few cases have been reported (35,36).…”

Early symptoms of autism spectrum disorder (ASD) in 1–8 year old children with sex chromosome trisomies (XXX, XXY, XYY), and the predictive value of joint attention

“…The current study aims to investigate the prospective impact of Sex Chromosome Trisomies (SCTs; XXX, XXY, XYY) on the appearance of early symptoms of Autism Spectrum Disorder (ASD), in children aged 1–8 years, with specific emphasis on the predictive value of Joint Attention on these ASD symptoms. The biological predisposition of SCTs allows us to study early social developmental pathways of a homogeneous group of children, and may be considered an ‘at risk’ group when it comes to neurobehavioral social adaptive development and related psychopathology [ 8 , 17 ], since the risk for ASD in this group has been found to be about 15–30% in children and adolescents [ 8 ]. The results of our study add to the understanding of the early prospective contribution of the extra X or Y chromosome on clinical risk for behavioral defined neurodevelopmental disorder such as ASD, and of early Joint Attention mechanisms predicting these ASD symptoms.…”

Renewal of the Neurophysiology of Language: Functional Neuroimaging

“…From a physiological standpoint, functional neuroimaging could prove a powerful tool for acquiring scientific insight into gene-brain-behavior links, which would provide an invaluable complement to more traditional research based on purely anatomical approaches to brain structures (326).…”