Aim We aimed to study tuberous sclerosis‐associated neuropsychiatric disorders (TAND) in children and adolescents with tuberous sclerosis complex (TSC). Method Retrospective and prospective cohort study conducted at a Paediatric Neurology Unit of an Italian Tertiary Care Hospital. Clinical and neuroimaging data were reviewed. Scores for neurological and epilepsy outcomes (Extended Glasgow Outcome Scale, Paediatric Version and Early Childhood Epilepsy Severity Scale modified), semi‐structured interviews (authorized Italian version of the TAND checklist and Vineland Adaptive Behavior Scales) and questionnaires (Child Behavior Checklist [CBCL]) were applied at last follow‐up. Results Thirty‐two patients with TSC (age range 1–19y) were enrolled. Eighty‐eight per cent had at least one TAND and 47% had intellectual disability. The TAND checklist showed internalizing problems in 25.8% of cases (vs 41.9% by CBCL), and externalizing problems in 41.9% (vs 9.7% by CBCL). TAND prevailed in patients with de novo mutation of TSC2, high tuber load, and severe neurological and epilepsy outcomes. Interpretation In our cohort, 78% of patients had more than four TAND behavioural problems; nevertheless, they did not show a constant and specific neuropsychiatric profile. Clinical, neurophysiological, and neuroradiological features were associated with several TAND. The TAND checklist appeared more effective than the CBCL, particularly in detecting externalizing problems. What this paper adds The Tuberous sclerosis‐associated neuropsychiatric disorders (TAND) checklist is an effective tool for TAND screening. The TAND checklist helps define psychopathological and neuropsychiatric aspects in paediatric patients with Tuberous sclerosis complex (TSC). TAND were found in 88% of patients with TSC, whilst 78% had more than four TAND. TAND distribution depends on different clinical and neuroradiological features.

An increased lifetime risk of epilepsy has been reported in neurofibromatosis type 1 (NF1) patients, ranging between 4% and 14%. To further analyze the correlation between NF1 and epilepsy, we retrospectively reviewed the epidemiologic, clinical, radiological, and molecular data of 784 unselected patients diagnosed with NF1 and referred to the neurofibromatosis outpatient clinics at the University Hospital of Padua. A crude prevalence of epilepsy of 4.7% was observed. In about 70% of cases, seizures arose in the context of neuroradiological findings, with the main predisposing factors being cerebral vasculopathies and hydrocephalus. In the absence of structural abnormalities, the prevalence of epilepsy was found to be 1.27%, which is approximately equal to the total prevalence in the general population. NF1 patients with seizures exhibit a higher incidence of intellectual disability and/or developmental delay, as well as of isolated learning disabilities. The comparison of causative NF1 mutations between the two groups did not reveal a specific genotype–phenotype correlation. Our data refine the current knowledge on epileptological manifestations in NF1 patients, arguing against the hypothesis that specific mechanisms, inherent to neurofibromin cellular function, might determine an increased risk of epilepsy in this condition.

Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. An ever-increasing amount of evidence suggests that such regulatory processes may play a pivotal role both in the initiation of pregnancy and in the later processes of embryonic and fetal development, thus determining long-term effects even in adult life. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal–fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we also recapitulate the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition, stress hormones, microbiome, and teratogens, focusing on their ability to cause epigenetic modifications in the gestational environment and ultimately in the fetus. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders.

Since the early 2000s, an ever-increasing subset of missense pathogenic variants in the ACTG1 gene has been associated with an autosomal-dominant, progressive, typically post-lingual non-syndromic hearing loss (NSHL) condition designed as DFNA20/26. ACTG1 gene encodes gamma actin, the predominant actin protein in the cytoskeleton of auditory hair cells; its normal expression and function are essential for the stereocilia maintenance. Different gain-of-function pathogenic variants of ACTG1 have been associated with two major phenotypes: DFNA20/26 and Baraitser–Winter syndrome, a multiple congenital anomaly disorder. Here, we report a novel ACTG1 variant [c.625G>A (p. Val209Met)] in an adult patient with moderate-severe NSHL characterized by a downsloping audiogram. The patient, who had a clinical history of slowly progressive NSHL and tinnitus, was referred to our laboratory for the analysis of a large panel of NSHL-associated genes by next generation sequencing. An extensive review of previously reported ACTG1 variants and their associated phenotypes was also performed.

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