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Judith L. Ross - One of the best experts on this subject based on the ideXlab platform.
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Decreased levels of γ-aminobutyric acid in temporal lobe of children with 47,XYY Syndrome
Neuroreport, 2021Co-Authors: Timothy P.l. Roberts, Judith Miller, Luke Bloy, Lisa Blaskey, Judith L. RossAbstract:47,XYY Syndrome (XYY) is a male sex chromosome disorder where subjects have one X chromosome and two copies of the Y chromosome. XYY is associated with a physical phenotype and carries increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD). Imbalance of excitation and inhibition has been proposed as a putative biological basis of disorders such as ASD [1-3] and several studies have reported atypical brain γ-aminobutyric acid (GABA) levels in this population. Given the male preponderance in the prevalence of ASD, the unique presence of the Y chromosome in males leads to the intriguing possibility of investigating boys with XYY Syndrome as a model of excess Y-chromosome genes. In this study, we investigated the associations of genotype and clinical phenotype with levels of GABA, estimated by regionally localized edited magnetic resonance spectroscopy in boys with 47, XYY Syndrome compared to age-matched typically developing (XY) peers. Overall, we observed a decrease in GABA levels in XYY vs. XY, which appeared more significant in the left compared to the right hemisphere. There was no additional significant modulation of GABA levels in XYY according to presence/absence of ASD diagnosis. Interestingly, a positive correlation between bilateral GABA levels and testosterone levels was observed in pubescent XY boys that was not observed in XYY. The inhibitory neurotransmitter GABA appears to be reduced in boys with 47,XYY, especially in the left hemisphere. Further, the typical association between GABA and testosterone levels, observed in older typically developing control boys was not evident in boys with 47,XYY. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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decreased levels of γ aminobutyric acid in temporal lobe of children with 47 XYY Syndrome
Neuroreport, 2021Co-Authors: Timothy P.l. Roberts, Judith Miller, Luke Bloy, Lisa Blaskey, Judith L. RossAbstract:BACKGROUND 47,XYY Syndrome (XYY) is a male sex chromosome disorder where subjects have one X chromosome and two copies of the Y chromosome. XYY is associated with a physical phenotype and carries increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD). Imbalance of excitation and inhibition has been proposed as a putative biological basis of disorders such as ASD [1-3] and several studies have reported atypical brain γ-aminobutyric acid (GABA) levels in this population. Given the male preponderance in the prevalence of ASD, the unique presence of the Y chromosome in males leads to the intriguing possibility of investigating boys with XYY Syndrome as a model of excess Y-chromosome genes. METHOD In this study, we investigated the associations of genotype and clinical phenotype with levels of GABA, estimated by regionally localized edited magnetic resonance spectroscopy in boys with 47, XYY Syndrome compared to age-matched typically developing (XY) peers. RESULTS Overall, we observed a decrease in GABA levels in XYY vs. XY, which appeared more significant in the left compared to the right hemisphere. There was no additional significant modulation of GABA levels in XYY according to presence/absence of ASD diagnosis. Interestingly, a positive correlation between bilateral GABA levels and testosterone levels was observed in pubescent XY boys that was not observed in XYY. CONCLUSION The inhibitory neurotransmitter GABA appears to be reduced in boys with 47,XYY, especially in the left hemisphere. Further, the typical association between GABA and testosterone levels, observed in older typically developing control boys was not evident in boys with 47,XYY.
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Auditory evoked response delays in children with 47,XYY Syndrome.
Neuroreport, 2019Co-Authors: Luke Bloy, Judith L. Ross, J. Christopher Edgar, Judith Miller, Lisa Blaskey, Timothy P.l. RobertsAbstract:47,XYY Syndrome (XYY) is a male sex chromosome disorder where individuals have an X chromosome and two copies of the Y chromosome. XYY is associated with a physical phenotype and carries increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD). Latencies of auditory evok
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Sensory Features as a Marker of Autism Spectrum Disorders.
Journal of autism and developmental disorders, 2019Co-Authors: Ebonee Bizzell, Judith L. Ross, Carly Rosenthal, Rachel Dumont, Roseann C. SchaafAbstract:We explored sensory features as distinguishing characteristics of Autism spectrum disorder (ASD). Four groups of males (n = 36): Six with 47, XYY Syndrome and ASD (XYY+ASD), six with 47, XYY Syndrome and no ASD (XYY−ASD), 12 with idiopathic ASD (ASD-I) and 12 typically developing (TYP). The short sensory profile (SSP) the sensory challenge protocol (SCP) were used to assess sensory features. SSP Total Score for the YY+ASD was significantly lower than the XYY−ASD (p = .002) and TYP (p < .001), but were not different from ASD-I (p = .714). The XYY+ASD group had significantly lower baseline heart rate variability during the SCP than TYP (p = .044). Findings provide preliminary support of sensory features as important in ASD diagnosis.
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Sex chromosomes and the brain: a study of neuroanatomy in XYY Syndrome.
Developmental medicine and child neurology, 2012Co-Authors: Daniel M. Bryant, Fumiko Hoeft, Song Lai, John Lackey, David P. Roeltgen, Judith L. Ross, Allan L. ReissAbstract:XYY Syndrome is a genetic disorder characterized by an additional Y chromosome. Affecting only individuals who are phenotypically male, XYY Syndrome is a common sex chromosome aneuploidy condition in humans, occurring in approximately one in 1000 live male births.1 XYY Syndrome has been associated with subtle physical features including tall stature2 and increased head circumference,3–5 though not all studies have observed the latter finding.6 XYY Syndrome is also associated with cognitive-behavioural deficits, most notably impairments in language and motor ability,3,5–7 and is thought to entail increased risk of autism spectrum disorders (ASDs).3,8–10 In contrast, Klinefelter Syndrome is a genetic disorder characterized by an additional X chromosome. Also affecting only individuals who are phenotypically male, Klinefelter Syndrome has an estimated prevalence of one in 600 live male births1 and often manifests with a characteristic physical phenotype, which includes reduced head circumference,6 tall stature, and hypogonadism.11 Individuals with Klinefelter Syndrome exhibit impairments in language and motor ability similar to those observed in XYY Syndrome,5 raising the question of why two disorders with identifiably disparate genetic bases produce partially overlapping cognitive phenotypes. The present study addressed this question by highlighting regional neuroanatomical similarities and disparities between the two groups. Though several neuroimaging studies have revealed abnormal brain structure associated with Klinefelter Syndrome, to our knowledge, only one neuroimaging study has specifically addressed XYY neuroanatomy.12 Gross neuroanatomical variation associated with Klinefelter Syndrome most prominently includes reduced total brain volume,12–14 though some report no significant difference.15,16 Other independently replicated anatomical imaging findings in Klinefelter Syndrome include reduced frontal and temporal grey matter13,14,17 and either increased or spared parietooccipital grey matter.17,18 In the present study, we used conceptually distinct approaches to compare the neuroanatomy of eight males with XYY, 31 males with Klinefelter Syndrome, and 36 typically developing males. First, we analysed total tissue volume using volumetric methods. Second, we explored patterns of regional grey matter and white matter difference using pattern classification analysis. We hypothesized that males with XYY Syndrome would have increased total tissue volume, given previous reports of increased head circumference in individuals with XYY Syndrome. Because of reports that males with XYY Syndrome exhibit impairments in language and motor ability similar to those exhibited in Klinefelter Syndrome, we also expected males with XYY Syndrome to exhibit patterns of regional brain variation more similar to those observed in males with Klinefelter Syndrome than in typically developing males.
Angela M Kaindl - One of the best experts on this subject based on the ideXlab platform.
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is microcephaly a so far unrecognized feature of XYY Syndrome
Meta Gene, 2014Co-Authors: Sylvie Nguyenminh, Christoph Buhrer, Christoph Hubner, Angela M KaindlAbstract:To the Editor: The 47,XYY Syndrome is a frequent sex chromosome aneuploidy in males occurring in approximately 1/1000 male newborns (Ross et al., 2012). Patients characteristically exhibit a weight, height and head circumference above average starting at birth (Geerts et al., 2003), which has been associated with an overexpression of growth-related genes (Geerts et al., 2003, Korenberg et al., 1994). Attention has been raised to the presentation of delayed speech development and language based learning disabilities, increased frequency of attention deficit problems as well as hyperactivity and impulsiveness (Lalatta et al., 2012, Evans et al., 1986). Here, we report a patient with a prenatally diagnosed 47,XYY karyotype who presented to our clinic at the age of 7 years with a secondary, early infantile microcephaly (Fig. 1). The index patient is the first child of healthy, unrelated parents. Amniocentesis was performed prenatally due to an increased nuchal fold, and chromosome analysis revealed a 47,XYY karyotype. A cesarean section was performed at 34 weeks of gestation due to preeclampsia with preterm labor and fetal heart rate abnormalities. At birth, the infant had a weight of 1930 g (40th centile), a length of 43 cm (40th centile) and a head circumference of 31 cm (50th centile). Birth was complicated by severe postnatal respiratory distress Syndrome (Apgar 3/2, umbilical artery pH 7.32), requiring surfactant administration and mechanical ventilation for 9 days. Pre- and postnatal laboratory findings including infection parameters, microbiologic testing and newborn screening for metabolic and endocrine diseases were unremarkable. The patient did not show clinical signs of hypoxic-ischemic encephalopathy in the newborn period with continually normal neurological examination. Furthermore, normal brain morphology was confirmed by repeated cranial ultrasound and the background activity was normal on electroencephalography with no signs of epileptic discharges. Cardiologic morphology and function and ophthalmologic investigations at birth and at follow-up appointments were normal. Fig. 1 Clinical phenotype of the patient. (A) Head circumferences of the index patient (head circumference chart according to longitudinal studies in Zurich, Switzerland from 1974 to 2009, Pediatrica 2011, Vol. 22, No. 1). (B) Picture of the index patient ... Microcephaly was noted at approximately 5 months of age (occipitofrontal head circumference (OFC) 40.5 cm, < 3rd centile). The motor milestones were normal, but a delay in speech development was noted. At the age of 7 years, the patient was presented in our clinic due to poor school performance and behavioral problems including, temper tantrums and aggressive behavior, refusal to perform tasks and an attention deficit that had become apparent shortly after school enrollment. A salient shyness with insecure behavior in a group setting and a negative self-perception were diagnosed in a psychological assessment. In the familial environment, the patient likewise exhibited outbursts of rage and refusal in reaction to frustrating events and an enormous fear of failure. Cognitive ability testing revealed intellectual impairment with learning disability (Hamburg-Wechsler Intelligence test for Children (HAWIK-IV): overall cognitive ability 79, verbal comprehension index 88, perceptual reasoning index 90, processing speed index 74 and working memory index 80) and marked difficulties in auditory discrimination and short-time memory. Clinical examination at age 7 was unremarkable except for a microcephaly (OFC 50 cm, < 3rd centile), a mild gait ataxia without further coordination deficit and a non-palpable left testis (body weight 15th centile, body length 40th centile). We confirmed a 47,XYY karyotype in a repeated chromosomal analysis and ruled out further microdeletions or -duplications through array CGH analysis (Microarray Kit 244A, Agilent Technologies, Santa Clara, USA) from the index patient. To our knowledge, we here report the first patient with a 47,XYY karyotype and a secondary, early infantile microcephaly rather than a normal head circumference or macrocephaly reported previously in this context (Nicolson et al., 1998, Fryns et al., 1995, Ratcliffe et al., 1994, Ottesen et al., 2010, Ratcliffe et al., 1979, Evans et al., 1986). Similarly, weight and height of our patient are in the lower normal range, while an increase in both body measurements has been reported for patients with XYY Syndrome (literature search in the NCBI and OMIM databases with the search terms ‘47,XYY’ or ‘sex chromosome abnormalities’ in combination with ‘head circumference’, ‘body measurements’, ‘centiles’, ‘growth’, ‘microcephaly’, ‘macrocephaly’ as well as ‘effect of chromosome abnormalities on growth’). Hypoxic-ischemic encephalopathy and exogenous causes of microcephaly such as in utero exposure to alcohol, malnutrition or perinatal infection were excluded. Genetic testing was repeated postnatally and complemented by an array CGH to exclude additional numerical chromosome aberrations or microdeletion or -duplication Syndromes that could cause the microcephaly in our index patient. Among the numerous genetic Syndromes associated with microcephaly, we specifically aimed at excluding a trisomy of chromosome 21, since this has been linked to both the 47,XYY karyotype (Fryns et al., 1995) and microcephaly (Korenberg et al., 1994). Underlying cardiologic dysfunction was excluded as a cause of dystrophy. Moreover, no severe asphyxia occurred as a cause of the patient´s secondary microcephaly. The pattern of behavioral problems reported in our patient is in line with the previously reported increased risk of impulsivity, poor adaptation to social situations and attention or hyperactivity disorder (Ross et al., 2012). The learning disability of our patient is concurrent with a previously reported prevalence of up to 80% in 47,XYY Syndrome (Geerts et al., 2003). Our index patient also showed a marked deficit in auditory discrimination, which might be a contributing factor to the high prevalence of language development delay in 47,XYY Syndrome (Geerts et al., 2003). In conclusion, our report shows that 47,XYY karyotype can be associated with a microcephaly and broadens the spectrum of clinical features. The behavioral problems described in our patient are in line with previous reports. Accordingly, clinicians may also consider an underlying 47,XYY Syndrome in a patient with the “typical pattern” of behavioral problems, a microcephaly and average or low body measurements. Further follow-up of children with 47,XYY karyotype born preterm will have to be undertaken to provide a reference of expectable body measurements.
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Is microcephaly a so-far unrecognized feature of XYY Syndrome?
Meta gene, 2014Co-Authors: Sylvie Nguyen-minh, Christoph Buhrer, Christoph Hubner, Angela M KaindlAbstract:To the Editor: The 47,XYY Syndrome is a frequent sex chromosome aneuploidy in males occurring in approximately 1/1000 male newborns (Ross et al., 2012). Patients characteristically exhibit a weight, height and head circumference above average starting at birth (Geerts et al., 2003), which has been associated with an overexpression of growth-related genes (Geerts et al., 2003, Korenberg et al., 1994). Attention has been raised to the presentation of delayed speech development and language based learning disabilities, increased frequency of attention deficit problems as well as hyperactivity and impulsiveness (Lalatta et al., 2012, Evans et al., 1986). Here, we report a patient with a prenatally diagnosed 47,XYY karyotype who presented to our clinic at the age of 7 years with a secondary, early infantile microcephaly (Fig. 1). The index patient is the first child of healthy, unrelated parents. Amniocentesis was performed prenatally due to an increased nuchal fold, and chromosome analysis revealed a 47,XYY karyotype. A cesarean section was performed at 34 weeks of gestation due to preeclampsia with preterm labor and fetal heart rate abnormalities. At birth, the infant had a weight of 1930 g (40th centile), a length of 43 cm (40th centile) and a head circumference of 31 cm (50th centile). Birth was complicated by severe postnatal respiratory distress Syndrome (Apgar 3/2, umbilical artery pH 7.32), requiring surfactant administration and mechanical ventilation for 9 days. Pre- and postnatal laboratory findings including infection parameters, microbiologic testing and newborn screening for metabolic and endocrine diseases were unremarkable. The patient did not show clinical signs of hypoxic-ischemic encephalopathy in the newborn period with continually normal neurological examination. Furthermore, normal brain morphology was confirmed by repeated cranial ultrasound and the background activity was normal on electroencephalography with no signs of epileptic discharges. Cardiologic morphology and function and ophthalmologic investigations at birth and at follow-up appointments were normal. Fig. 1 Clinical phenotype of the patient. (A) Head circumferences of the index patient (head circumference chart according to longitudinal studies in Zurich, Switzerland from 1974 to 2009, Pediatrica 2011, Vol. 22, No. 1). (B) Picture of the index patient ... Microcephaly was noted at approximately 5 months of age (occipitofrontal head circumference (OFC) 40.5 cm,
Ebonee Bizzell - One of the best experts on this subject based on the ideXlab platform.
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Sensory Features as a Marker of Autism Spectrum Disorders
Journal of Autism and Developmental Disorders, 2019Co-Authors: Ebonee Bizzell, Judith Ross, Carly Rosenthal, Rachel Dumont, Roseann SchaafAbstract:We explored sensory features as distinguishing characteristics of Autism spectrum disorder (ASD). Four groups of males (n = 36): Six with 47, XYY Syndrome and ASD (XYY+ASD), six with 47, XYY Syndrome and no ASD (XYY−ASD), 12 with idiopathic ASD (ASD-I) and 12 typically developing (TYP). The short sensory profile (SSP) the sensory challenge protocol (SCP) were used to assess sensory features. SSP Total Score for the YY+ASD was significantly lower than the XYY−ASD (p = .002) and TYP (p
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Sensory Features as a Marker of Autism Spectrum Disorders.
Journal of autism and developmental disorders, 2019Co-Authors: Ebonee Bizzell, Judith L. Ross, Carly Rosenthal, Rachel Dumont, Roseann C. SchaafAbstract:We explored sensory features as distinguishing characteristics of Autism spectrum disorder (ASD). Four groups of males (n = 36): Six with 47, XYY Syndrome and ASD (XYY+ASD), six with 47, XYY Syndrome and no ASD (XYY−ASD), 12 with idiopathic ASD (ASD-I) and 12 typically developing (TYP). The short sensory profile (SSP) the sensory challenge protocol (SCP) were used to assess sensory features. SSP Total Score for the YY+ASD was significantly lower than the XYY−ASD (p = .002) and TYP (p < .001), but were not different from ASD-I (p = .714). The XYY+ASD group had significantly lower baseline heart rate variability during the SCP than TYP (p = .044). Findings provide preliminary support of sensory features as important in ASD diagnosis.
Shoichi Inaba - One of the best experts on this subject based on the ideXlab platform.
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Conditioning with targeted busulfan for autologous peripheral blood stem cells transplantation for acute myelogenous leukemia in an XYY male.
American journal of hematology, 2004Co-Authors: Eriko Sada, Hideho Henzan, Ryoko Ohtani, Ken Takase, Toshihiro Miyamoto, Takahiro Fukuda, Koji Nagafuji, Keita Yamauchi, Yasushi Takamatsu, Shoichi InabaAbstract:We report herein a 19-year-old Japanese male with XYY Syndrome who developed acute myelogenous leukemia. During three courses of cytotoxic chemotherapy, he suffered repeated hepatic and renal insufficiencies, possibly related to latent dysfunction from the XYY Syndrome. The patient was treated with granulocyte colony-stimulating factor combined with etoposide, cytarabine, and busulfan (the latter adjusted to a targeting dose) followed by autologous peripheral blood stem cell transplantation. He had no severe regimen-related toxicities and is now free of leukemia.
Yoshitomo Mutou - One of the best experts on this subject based on the ideXlab platform.
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Severe regimen-related toxicity occurring in a patient with XYY Syndrome receiving allogeneic peripheral blood stem cell transplantation.
Annals of hematology, 2002Co-Authors: S. Shibata, Masahiro Kami, Yukiko Kishi, Tamae Hamaki, J Ueyama, Shigesaburo Miyakoshi, Shinichi Morinaga, N. Hirabayashi, Yoshinobu Kanda, Yoshitomo MutouAbstract:A 23-year-old man with chronic myelocytic leukemia (CML) in the first chronic phase underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-identical sibling. Pretransplant evaluations showed that he had a low risk of transplantation-related mortality and that the interval between the diagnosis of CML and PBSCT was only 6 months. However, he developed a variety of complications, including acute renal failure requiring hemodialysis, severe hepatic damage, hemorrhagic cystitis, and gastrointestinal hemorrhage leading to hypovolemic shock. Pathological examination of the colonic mucosa showed vascular endothelial damage and thrombotic lesions, leading to the diagnosis of thrombotic microangiopathy. Later, we found that he had the constitutional abnormality XYY. XYY Syndrome is a frequent congenital abnormality, and mental disorders and congenital abnormalities of kidney and liver are common manifestations. Considering his clinical course, it was interesting that complications were severe in the organs which are frequently involved in cases of XYY Syndrome. These organs may have poor function or poor reserves and may be more vulnerable to endothelial damage caused by high-dose cytotoxic chemotherapy. Patients with XYY Syndrome might have a high risk of transplantation-related mortality.