Effects of sex chromosome dosage on corpus callosum morphology in supernumerary sex chromosome aneuploidies.

BackgroundSupernumerary sex chromosome aneuploidies (sSCA) are characterized by the presence of one or more additional sex chromosomes in an individual's karyotype; they affect around 1 in 400 individuals. Although there is high variability, each sSCA subtype has a characteristic set of cognitive and physical phenotypes. Here, we investigated the differences in the morphometry of the human corpus callosum (CC) between sex-matched controls 46,XY (N =99), 46,XX (N =93), and six unique sSCA karyotypes: 47,XYY (N =29), 47,XXY (N =58), 48,XXYY (N =20), 47,XXX (N =30), 48,XXXY (N =5), and 49,XXXXY (N =6).MethodsWe investigated CC morphometry using local and global area, local curvature of the CC boundary, and between-landmark distance analysis (BLDA). We hypothesized that CC morphometry would vary differentially along a proposed spectrum of Y:X chromosome ratio with supernumerary Y karyotypes having the largest CC areas and supernumerary X karyotypes having significantly smaller CC areas. To investigate this, we defined an sSCA spectrum based on a descending Y:X karyotype ratio: 47,XYY, 46,XY, 48,XXYY, 47,XXY, 48,XXXY, 49,XXXXY, 46,XX, 47,XXX. We similarly explored the effects of both X and Y chromosome numbers within sex. Results of shape-based metrics were analyzed using permutation tests consisting of 5,000 iterations.ResultsSeveral subregional areas, local curvature, and BLDs differed between groups. Moderate associations were found between area and curvature in relation to the spectrum and X and Y chromosome counts. BLD was strongly associated with X chromosome count in both male and female groups.ConclusionsOur results suggest that X- and Y-linked genes have differential effects on CC morphometry. To our knowledge, this is the first study to compare CC morphometry across these extremely rare groups

Deficits in Implicit Attention to Social Signals in Schizophrenia and High Risk Groups: Behavioural Evidence from a New Illusion

Background An increasing body of evidence suggests that the apparent social impairments observed in schizophrenia may arise from deficits in social cognitive processing capacities. The ability to process basic social cues, such as gaze direction and biological motion, effortlessly and implicitly is thought to be a prerequisite for establishing successful social interactions and for construing a sense of "social intuition." However, studies that address the ability to effortlessly process basic social cues in schizophrenia are lacking. Because social cognitive processing deficits may be part of the genetic vulnerability for schizophrenia, we also investigated two groups that have been shown to be at increased risk of developing schizophrenia-spectrum pathology: first-degree relatives of schizophrenia patients and men with Klinefelter syndrome (47,XXY). Results We compared 28 patients with schizophrenia, 29 siblings of patients with schizophrenia, and 29 individuals with Klinefelter syndrome with 46 matched healthy control subjects on a new paradigm. This paradigm measures one's susceptibility for a bias in distance estimation between two agents that is induced by the implicit processing of gaze direction and biological motion conveyed by these agents. Compared to control subjects, patients with schizophrenia, as well as siblings of patients and Klinefelter men, showed a lack of influence of social cues on their distance judgments. Conclusions We suggest that the insensitivity for social cues is a cognitive aspect of schizophrenia that may be seen as an endophenotype as it appears to be present both in relatives who are at increased genetic risk and in a genetic disorder at risk for schizophrenia-spectrum psychopathology. These social cue-processing deficits could contribute, in part, to the difficulties in higher order social cognitive tasks and, hence, to decreased social competence that has been observed in these groups

X marks the spot: Structural and functional brain mapping in a genetically defined group at high risk of autism symptoms (47,XXY), and a comparison with idiopathic autism spectrum disorder

Klinefelter syndrome (47,XXY) is associated with a wide range of behavioral problems, including autism symptomatology. In the current thesis, brain structure and function were assesed in boys with 47,XXY, boys with idiopathic autism spectrum disorder, and non-clinical controls, using multiple imaging techniques. The goal was to assess the mechanisms underlying social dysfunction in 47,XXY, and to investigate to what degree these mechanisms differ from those in individuals with idiopathic autism. The results show that individuals with 47,XXY show characteristic deviations in brain structure and function associated with higher order cognitive functions, social emotional information processing, and language processing. Additionally, while boys with 47,XXY show considerable overlap with boys with idiopathic ASD in autism symptomatology, there are specific differences in the underlying neural mechanisms that revolve around the frontal lobes and insular cortices. These findings may have implications for intervention studies (e.g. focused on real time fMRI neurofeedback), as well as clinical practice. It may impact the selection of mental health care strategies that take into account this variability in mechanisms underlying social dysfunction in individuals with autism spectrum disorder.Development Psychopathology in context: clinical setting

Murrosiän ajoittuminen Klinefelterin oireyhtymässä

Klinefelterin oireyhtymä (KS) on yleisin sukupuolikromosomipoikkeavuus, jossa pojalla on yksi tai useampi ylimääräinen X-sukupuolikromosomi perinteisten X- ja Y-sukupuolikromosomien lisäksi. Mosaiikkimuotoisessa oireyhtymässä osassa soluista on ylimääräinen X-kromosomi ja osassa normaali määrä sukupuolikromosomeja. Klinefelterin oireyhtymä saattaa tulla esiin murrosiässä pienen kiveskoon, rintarauhasen liikakasvun tai erilaisten oppimisvaikeuksien kautta. Aikuisuudessa KS-miehillä esiintyy usein androgeenivajavuutta. KS-poikien murrosiän ajoittumisesta saatava tieto on ristiriitaista. Eurooppalaisen käsityksen mukaan KS-poikien murrosiän ajoittuminen on normaali, kun taas joidenkin Pohjois-Amerikkalaisten tutkimusten mukaan se on viivästynyt. Tavoitteenani oli selvittää klassisen Klinefelterin oireyhtymän XXY-karyotyypin omaavien poikien murrosiän ajoittumista. Keräsin anonyymisoidut potilastiedot KS-poikien murrosiän etenemisestä HUS Lasten ja nuorten toimialalta Klinefelter-diagnoosihaulla vuosilta 2004–2018. Kasvutietojen pohjalta selvitin KS-poikien kasvupyrähdyksen ajoittumista sekä kasvunopeutta kasvupyrähdyksessä. Tämän lisäksi kirjasin ylös tiedot Tannerin P- ja G-puberteettiasteiden ajoittumisesta sekä kivesten mitoista murrosiässä. Analyyseihin hyväksyttiin havainnot ennen testosteronikorvaushoitojen aloittamista. Vertailuaineistona käytin toisaalta Pekka Ojajärven väitöskirjaa Suomalaisen lapsen murrosikä. Toisaalta asetin havainnot P- ja G-asteiden ajoittumisesta äskettäin julkaistuun tanskalaiseen puberteettinomogrammiin. KS-poikien kasvupyrähdyksen ajoittuminen sekä kasvunopeus kasvupyrähdyksessä eivät poikenneet merkitsevästi suomalaisen vertailuaineiston tuloksista. Myös puberteettinomogrammilla P- ja G-asteiden ajoittuminen oli normaalin rajoissa. Nämä tulokset viittaavat siihen, että KS-poikien murrosiän ajoittuminen ja tempo ovat normaalit

Detección temprana del síndrome de XYY mediante la cuantificación de la dosis génica de SHOX, VAMP7 y SRY por QPCR en muestras de sangre en papel filtro

Las aneuploidías de cromosomas sexuales son las aberraciones cromosómicas más comunes en los humanos, dentro de este grupo se encuentra el Síndrome de Turner, la Polisomía del X, el Síndrome de Klinefelter y el Síndrome XYY. Este estudio está dedicado a describir las características clínicas de los pacientes detectados por medio de un programa de tamiz para aneuploidías de cromosomas sexuales. Se trata de un estudio descriptivo, transversal y ciego en neonatos sanos de dos hospitales públicos de los servicios de salud del estado de Nuevo León. Aquellos con dosis génica sugestiva de síndrome XYY fueron remitidos al Departamento de Genética para cariotipo y evaluación clínica. Siete pacientes con dosis génica sugestiva fueron detectados, en 4 de ellos se obtuvo un cariotipo 47,XYY confirmando el diagnostico, en dos más el cariotipo fue masculino normal (46,XY) y el restante no continuo el protocolo. Los 4 pacientes confirmados mostraron dismorfias menores que no fueron reconocidas hasta después del estudio confirmatorio, como hipertelorismo y micropene, siendo este último una característica no reportada previamente como parte del síndrome. Estas dismorfias menores pueden ser el punto de partida para sospechar Síndrome XYY, lo cual permitiría un diagnóstico temprano, la implementación de un seguimiento personalizado para la búsqueda intencionada de complicaciones relacionadas al mismo lo cual a su vez conduciría a un manejo oportuno que mejore la calidad de vida de cada paciente