Correlation of CAG repeat length between the maternal and paternal allele of the Huntingtin gene: evidence for assortative mating

Triplet repeats contribute to normal variation in behavioral traits and when expanded, cause brain disorders. While Huntington's Disease is known to be caused by a CAG triplet repeat in the gene Huntingtin, the effect of CAG repeats on brain function below disease threshold has not been studied. The current study shows a significant correlation between the CAG repeat length of the maternal and paternal allele in the Huntingtin gene among healthy subjects, suggesting assortative mating

Behavioral Effects of Congenital Ventromedial Prefrontal Cortex Malformation

Background: A detailed behavioral profile associated with focal congenital malformation of the ventromedial prefrontal cortex (vmPFC) has not been reported previously. Here we describe a 14 year-old boy, B.W., with neurological and psychiatric sequelae stemming from focal cortical malformation of the left vmPFC. Case Presentation: B.W.'s behavior has been characterized through extensive review Patience of clinical and personal records along with behavioral and neuropsychological testing. A central feature of the behavioral profile is severe antisocial behavior. He is aggressive, manipulative, and callous; features consistent with psychopathy. Other problems include: egocentricity, impulsivity, hyperactivity, lack of empathy, lack of respect for authority, impaired moral judgment, an inability to plan ahead, and poor frustration tolerance. Conclusions: The vmPFC has a profound contribution to the development of human prosocial behavior. B.W. demonstrates how a congenital lesion to this cortical region severely disrupts this process

Morphology of the ventral frontal cortex: Relationship to femininity and social cognition

Females have been shown in a number of studies to be more adept in social perception compared with males. In addition, studies have reported that brain regions important in interpretation of nonverbal social cues, such as the ventral frontal cortex (VFC), are morphologically different between genders. To investigate the relationship between the structure of the VFC and social cognition, gray matter volume and surface area of the VFC were measured on magnetic resonance imaging (MRI) scans from 30 men and 30 women matched for age and IQ. The VFC was subdivided into the orbitofrontal cortex (OFC) and the straight gyrus (SG). The SG, but not the OFC, was proportionately larger in women. A subset of subjects was administered the Interpersonal Perception Task (IPT), a test of social perceptiveness, and the Personal Attributes Questionnaire (PAQ), a scale of femininity and masculinity. Identification with more feminine traits on the PAQ correlated with greater SG gray matter volume and surface area. In addition, higher degrees of femininity correlated with better performance on the IPT. Taken together, these data suggest a complex relationship between femininity, social cognition, and the structure of the SG

Consensus-based care recommendations for adults with myotonic dystrophy type 1

Purpose of review Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit. Recent findings The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations. Summary The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments. Described as “one of the more variable diseases found in medicine,” myotonic dystrophy type 1 (DM1) is an autosomal dominant, triplet-repeat expansion disorder that affects somewhere between 1:3,000 and 1:8,000 individuals worldwide.1 There is a modest association between increased repeat expansion and disease severity, as evidenced by the average age of onset and overall morbidity of the condition. An expansion of over 35 repeats typically indicates an unstable and expanding mutation. An expansion of 50 repeats or higher is consistent with a diagnosis of DM1. DM1 is a multisystem and heterogeneous disease characterized by distal weakness, atrophy, and myotonia, as well as symptoms in the heart, brain, gastrointestinal tract, endocrine, and respiratory systems. Symptoms may occur at any age. The severity of the condition varies widely among affected individuals, even among members of the same family. Comprehensive evidence-based guidelines do not currently exist to guide the treatment of DM1 patients. As a result, the international patient community reports varied levels of care and care quality, and difficulty accessing care adequate to manage their symptoms, unless they have access to multidisciplinary neuromuscular clinics. Consensus-based care recommendations can help standardize and improve the quality of care received by DM1 patients and assist clinicians who may not be familiar with the significant variability, range of symptoms, and severity of the disease. Care recommendations can also improve the landscape for clinical trial success by eliminating some of the inconsistencies in patient care to allow more accurate understanding of the benefit of potential therapies

Autonomic Changes in Juvenile-Onset Huntington’s Disease

Patients with adult-onset Huntington’s Disease (AOHD) have been found to have dysfunction of the autonomic nervous system that is thought to be secondary to neurodegeneration causing dysfunction of the brain–heart axis. However, this relationship has not been investigated in patients with juvenile-onset HD (JOHD). The aim of this study was to compare simple physiologic measures between patients with JOHD (n = 27 participants with 64 visits) and participants without the gene expansion that causes HD (GNE group; n = 259 participants with 395 visits). Using data from the Kids-JOHD study, we compared mean resting heart rate (rHR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) between the JOHD and GNE groups. We also divided the JOHD group into those with childhood-onset JOHD (motor diagnosis received before the age of 13, [n = 16]) and those with adolescent-onset JOHD (motor diagnosis received at or after the age of 13 [n = 11]). We used linear mixed-effects models to compare the group means while controlling for age, sex, and parental socioeconomic status and including a random effect per participant and family. For the primary analysis, we found that the JOHD group had significant increases in their rHR compared to the GNE group. Conversely, the JOHD group had significantly lower SBP compared to the GNE group. The JOHD group also had lower DBP compared to the GNE group, but the results did not reach significance. SBP and DBP decreased as disease duration of JOHD increased, but rHR did not continue to increase. Resting heart rate is more sensitive to changes in autonomic function as compared to SBP. Therefore, these results seem to indicate that early neurodegenerative changes of the central autonomic network likely lead to an increase in rHR while later progression of JOHD leads to changes in blood pressure. We hypothesize that these later changes in blood pressure are secondary to neurodegeneration in brainstem regions such as the medulla

Ventral frontal cortex in children: morphology, social cognition and feminity/masculinity

The ventral frontal cortex (VFC) has been shown to differ morphologically between sexes. Social cognition, which many studies demonstrate involves the VFC, also differs between sexes, with females being more adept than males. In a previous study of subregions of the VFC in our lab, in an adult population, size of the straight gyrus (SG) but not the orbitofrontal cortex (OFC), differed between sexes and correlated with better performance on a test of social cognition and with greater identification with feminine characteristics. To investigate the relationship between VFC structure and social cognition in children, VFC gray matter volumes were measured on MRIs from 37 boys and 37 girls aged 7 to 17. The VFC was subdivided into the OFC and SG. Subjects were also administered a test of social perceptiveness and a rating scale of femininity/masculinity. In contrast to our findings in adults, the SG was slightly smaller in girls than boys. In girls, but not boys, smaller SG volumes significantly correlated with better social perception and higher identification with feminine traits. No volume differences by sex or significant correlations were found with the OFC. These data suggest a complex relationship between femininity, social cognition and SG morphology

Arithmetical calculation and related neuropsychological skills in subjects with isolated oral clefts.

OBJECTIVE: The current study examined whether the arithmetical calculation skills of children, adolescents, and young adults with isolated cleft of the lip and/or palate (iCL/P) differ significantly from unaffected control participants. Comparisons of potential neuropsychological predictors of arithmetical calculation were also conducted to determine whether these variables differ significantly for participants with iCL/P. METHOD: Participants (N = 176; 93 iCL/P and 83 Control) ranged in age from 7 to 26 years old. A standardized battery of achievement and neuropsychological skills was administered. Between group differences on math achievement was assessed through a univariate analysis of covariance. Relationships between neuropsychological measures and math achievement were analyzed separately for participants with iCL/P and controls through hierarchical linear regressions. RESULTS: Arithmetical calculation was significantly lower for the iCL/P group. Rapid naming, sustained attention, and visual-spatial organization were significant predictors for the iCL/P group; rapid naming was the lone variable that was significantly more predictive of arithmetical calculation for the iCL/P group than for control participants. CONCLUSIONS: These results suggest that inefficient verbal label retrieval related to short-term memory (STM) deficits underlie the calculation difficulties of individuals with iCL/P. These findings have implications for approaches to remediation, as well as future research. (PsycINFO Database Recor

The Association between CAG Repeat Length and Age of Onset of Juvenile-Onset Huntington’s Disease

There is a known negative association between cytosine–adenine–guanine (CAG) repeat length and the age of motor onset (AMO) in adult-onset Huntington’s Disease (AOHD). This relationship is less clear in patients with juvenile-onset Huntington’s disease (JOHD), however, given the rarity of this patient population. The aim of this study was to investigate this relationship amongst a relatively large group of patients with JOHD using data from the Kids-JOHD study. Additionally, we analyzed data from the Enroll-HD platform and the Predict-HD study to compare the relationship between CAG repeat length and AMO amongst patients with AOHD to that amongst patients with JOHD using linear regression models. In line with previous reports, the variance in AMO that was predicted by CAG repeat length was 59% (p < 0.0001) in the Predict-HD study and 57% from the Enroll-HD platform (p < 0.0001). However, CAG repeat length predicted 84% of the variance in AMO amongst participants from the Kids-JOHD study (p < 0.0001). These results indicate that there may be a stronger relationship between CAG repeat length and AMO in patients with JOHD as compared to patients with AOHD. These results provide additional information that may help to model disease progression of JOHD, which is beneficial for the planning and implementation of future clinical trials

Masculinity/Femininity Predicts Brain Volumes in Normal Healthy Children

Previous research has shown sex differences in brain morphology (De Bellis et al., 2001). However, these studies have not taken gender into account. Gender is a phenotype that describes behavior. In this study, we examined the relationship between gender, sex, and brain volumes in children. One hundred and eight children ages 7 to 17 were administered the Children\u27s Sex Role Inventory (Boldizar, 1991) and obtained volumetric brain data via magnetic resonance imaging (MRI). We found that, in the frontal lobe, higher masculinity predicted greater volumes of white matter. Also, in the temporal lobe, higher femininity predicted greater volumes of gray matter