Case Series: Neurobehavioral Profile of Adolescents with PTEN Hamartoma Tumor Syndrome.

Background: PTEN Hamartoma Tumor Syndrome (PHTS) is a rare genetic condition caused by germline mutations in the phosphatase and tensin homologue (PTEN) gene with a phenotype that includes macrocephaly, cancer predisposition, developmental delay, increased risk for autism spectrum disorder (ASD), and learning difficulties. Studies characterizing neurobehavioral profiles are limited. Methods: This single-site, retrospective case series was completed in children who have PHTS followed in a cancer predisposition clinic. Demographic and clinical, data were abstracted from the medical record for 12 patients (mean age at clinic entry = 8.83 years; 42% female). Neuropsychological data were abstracted for 3 of 12 patients that were referred for testing (17-year-old female with attention-deficit/hyperactivity disorder [ADHD]; 15-year-old male with academic concerns and ASD, 12-year-old male with academic concerns). Results: Of the 12 patients, macrocephaly was present in 100%, 58% had developmental delays during early childhood, and 17% had an ASD diagnosis. Results from neuropsychological testing showed Borderline to Average range global intellectual functioning (Standard Score range: 77 to 95) along with deficits in non-verbal reasoning, visual-motor integration, math achievement, and caregiver-rated adaptive skills. Conclusion: Individuals with PHTS may present with cognitive difficulties that impact everyday functioning, with or without a neurodevelopmental diagnosis. Routine neurocognitive assessment should be considered in management guidelines.

Variations in brain morphometry among healthy preschoolers born preterm.

BACKGROUND: Preterm birth is associated with an increased risk of neonatal brain injury, which can lead to alterations in brain maturation. Despite being born without the most significant medical consequences of preterm birth, infants born early remain at increased risk for subtle brain injury that affects future neurodevelopment and functioning. AIMS: To investigate the gray matter morphometry measures of cortical thickness, cortical surface area, and sulcal depth using MRI at 5 years of age in healthy children born preterm. STUDY DESIGN: Cohort study. SUBJECTS: Participants were 52 children born preterm (<33 weeks gestational age) and 37 children born full term. OUTCOME MEASURES: Cortical segmentation and calculation of morphometry measures were completed using FreeSurfer version 5.3.0 and compared between groups using surface-based, voxel-wise analyses. RESULTS: The preterm group had a significantly thinner cortex in temporal and parietal regions while cortical thickness was significantly larger within occipital and inferior frontal regions. Surface area was significantly reduced within the fusiform gyrus. Sulcal depth was significantly lower within the posterior parietal and inferior temporal regions but greater in the middle temporal and medial parietal regions. CONCLUSIONS: Regional differences were found between preschoolers born preterm and full term in cortical thickness, surface area, and sulcal depth. Cortical thickness differences primarily overlapped with regions found in previous studies of older children and adults. Differences in sulcal depth may represent additional areas of maturational differences in preterm children. These findings likely represent a combination of delayed maturation and permanent alterations caused by the perinatal processes associated with preterm birth.

Mathematics ability and related skills in preschoolers born very preterm.

Children born very preterm (VPT) are at risk for academic, behavioral, and/or emotional problems. Mathematics is a particular weakness and better understanding of the relationship between preterm birth and early mathematics ability is needed, particularly as early as possible to aid in early intervention. Preschoolers born VPT (n = 58) and those born full term (FT; n = 29) were administered a large battery of measures within 6 months of beginning kindergarten. A multiple-mediation model was utilized to characterize the difference in skills underlying mathematics ability between groups. Children born VPT performed significantly worse than FT-born children on a measure of mathematics ability as well as full-scale IQ, verbal skills, visual-motor integration, phonological awareness, phonological working memory, motor skills, and executive functioning. Mathematics was significantly correlated with verbal skills, visual-motor integration, phonological processing, and motor skills across both groups. When entered into the mediation model, verbal skills, visual-motor integration, and phonological awareness were significant mediators of the group differences. This analysis provides insights into the pre-academic skills that are weak in preschoolers born VPT and their relationship to mathematics. It is important to identify children who will have difficulties as early as possible, particularly for VPT children who are at higher risk for academic difficulties. Therefore, this model may be used in evaluating VPT children for emerging difficulties as well as an indicator that if other weaknesses are found, an assessment of mathematics should be conducted.