Tatton‐Brown–Rahman syndrome (TBRS) or DNMT3A‐overgrowth syndrome is characterized by overgrowth and intellectual disability associated with minor dysmorphic features, obesity, and behavioral ...problems. It is caused by variants of the DNMT3A gene. We report four patients with this syndrome due to de novo DNMT3A pathogenic variants, contributing to a deeper understanding of the genetic basis and pathophysiology of this autosomal dominant syndrome. Clinical and magnetic resonance imaging assessments were also performed. All patients showed corpus callosum anomalies, small posterior fossa, and a deep left Sylvian fissure; as well as asymmetry of the uncinate and arcuate fascicles and marked increased cortical thickness. These results suggest that structural neuroimaging anomalies have been previously overlooked, where corpus callosum and brain tract alterations might be unrecognized neuroimaging traits of TBRS syndrome caused by DNMT3A variants.
ANO3 and early-onset dyskinetic encephalopathy Jiménez de Domingo, Ana; Lopez-Martín, Sara; Albert, Jacobo ...
European journal of medical genetics,
December 2020, 2020-Dec, 2020-12-00, 20201201, Volume:
63, Issue:
12
Journal Article
Peer reviewed
Mutations in the ANO3 gene have been associated with autosomal dominant craniocervical dystonia. However, little else is known about the genotype-phenotype characteristics of this disorder. Here we ...describe a 3 years-old girl with distal myoclonic dystonia. Whole exome sequencing in trio revealed a de novo missense ANO3 variant not previously described in international databases. A global psychomotor regression was observed once dystonia was present. Brain MRI changes paralleled these findings: whereas MRI at the age of 18 months was normal, mild brain and cerebellar atrophy was observed 18 months later. These results suggest that missense mutations in ANO3 may underlie complex disorders particularly characterized by early psychomotor regression and dystonia.
Bi-allelic mutations in the TUBGCP4 gene have been recently associated with autosomal recessive microcephaly with chorioretinopathy. However, little is known about the genotype-phenotype ...characteristics of this disorder. Here, we describe a 5-year-old male patient with autism and a normal occipitofrontal circumference. No retinal abnormalities were observed. Brain MRI revealed the presence of enlarged sheaths of both tortuous optic nerves; both eyes had shorter axial lengths. Whole-exome sequencing in trio revealed synonymous TUBGCP4 variants in homozygous state: c.1746G>T; p.Leu582=. This synonymous variant has been previously described and probably leads to skipping of exon 16 of TUBGCP4. These results broaden the clinical spectrum of this new syndrome and suggest that TUBGCP4 bi-allelic mutations may underlie complex neurodevelopmental disorders.
The impact of ADHD on reading Sánchez-Carmona, Alberto J; Albert, Jacobo; López-Martín, Sara ...
Medicina,
04/2023, Volume:
83 Suppl 2
Journal Article
Peer reviewed
Beyond the frequent coexistence of attention deficit hyperactivity disorder (ADHD) and reading disorder (dyslexia), the present review aims to examine the available empirical evidence on how ADHD ...negatively impacts on learning to read. Existing data suggest that the presence of the disorder (especially inattention symptoms), may affect i) the correct acquisition of reading, either directly or through its influence on the precursors to reading; ii) decoding skills themselves (reading accuracy and fluency), both directly and indirectly through its influence on cognitive processes such as distractibility or executive functions; and iii) reading comprehension, probably indirectly through the executive and verbal memory difficulties characteristic of ADHD. These findings have important implications for better characterizing and intervening on reading difficulties in ADHD, whether clinical or subclinical.
Early B cell factor 3 (EBF3) is a transcription factor involved in brain development. Heterozygous, loss-of-function mutations in EBF3 have been reported in an autosomal dominant neurodevelopmental ...syndrome characterized by hypotonia, ataxia, and developmental delay (sometimes described as “HADD”s). We report 2 unrelated cases with novel de novo EBF3 mutations: c.455G>T (p.Arg152Leu) and c.962dup (p.Tyr321*) to expand the genotype/phenotype correlations of this disorder; clinical, neuropsychological, and MRI studies were used to define the phenotype. IQ was in the normal range and diffusion tensor imaging revealed asymmetric alterations of the longitudinal fasciculus in both cases. Our results demonstrate that EBF3 mutations can underlie neurodevelopmental disorders without intellectual disability. Long tract abnormalities have not been previously recognized and suggest that they may be an unrecognized and characteristic feature in this syndrome.
Advances in genetics have been able to support the clinical suspicion on the large hereditary component of most of these neurodevelopmental disorders (NDD). Initial studies on heritability, linkage ...or association showed from the beginning the great contribution of genotypic variation to the clinic in general, and to NDD in particular. The effectiveness of genetic studies in clinical practice, targeted to aetiological diagnosis, should not be ignored. Most of these are protocolized in the study of disorders such as intellectual disability and autism; within these, the array comparative genomic hybridization have supported a greater diagnostic effectiveness with respect to historical cytogenetic techniques (3 vs. 10% respectively). However, the irruption and success of molecular genetic sequencing techniques, particularly the exome and genome in trio, analyzing the parents (diagnostic rates of 30-50%), are conditioning the modification of the genetic algorithms in the diagnosis of different NDD. The greater knowledge of causal variants in intellectual disability and autism is also modifying the polygenic theoretical models established to date.
Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent disorders in the child and adolescent population, with a known impact on learning, social relations and quality of life. ...However, the lifestyle habits of patients with this disorder have been poorly studied.
A total of 160 children and adolescents, aged between 6 and 16 years, participated in the study. Half of them were treatment-naïve patients with a clinical diagnosis of ADHD according to DSM-IV-TR criteria, and without comorbidities. The remaining 80 participants were typically developing (TD) controls without known neurodevelopmental or psychiatric disorders. Parents of all participants completed a questionnaire about their children´s lifestyle habits (e.g, daily hours of sleep, media use and study).
The groups had a similar socioeconomic background and did not differ with respect to age and sex distribution. However, patients with ADHD spent more time than TD children studying, and less time watching TV, playing video games, using computers and playing with other people. They also slept fewer hours per night than children and adolescents with TD. ADHD and TD groups spent similar time reading, listening to music and playing sports.
The results of this study suggest that children and adolescents with ADHD have different lifestyle habits compared to age- and sex-matched controls. These findings are not explained by comorbid disorders or medication/ psychological treatment.
Abstract Background The Gamma-knife technique is a safe and effective option for the treatment of hypothalamic hamartomas that produce epileptic seizures refractory to medical treatment and/or ...serious behavioral disorders. After this type of radiosurgery, an adequate symptomatic control is normally achieved, with notable decrease or even disappearance of the seizures. Radiological changes, such as a decrease in the size of the tumor or adjacent edema secondary to non-necrotizing radioinduced inflammatory reaction are unusual consequences. Side effects and neurological complications are also rare events. Case presentation This report describe an unusual case of complete radiological resolution of a hypothalamic hamartoma as well as neurological complications after Gamma-knife surgery (receiving 13 Gy to the 85% isodose line, 1 cm3 of tumor volume) in a 8-year-old boy who suffered from severe refractory seizures. After radiosurgery, the patient experienced a notable improvement in his symptoms, achieving seizure cessation within 3 months. However, 4 months after the procedure he presented drowsiness, fever and decreased level of consciousness due to a direct effect on the hypothalamus with local and regional edema secondary to the radiosurgery that was performed. He was successfully treated with corticosteroids (with a total duration of 11 months), and twelve months after the surgery, complete disappearance of both the nodular lesion and the secondary edema was observed. The patient remains seizure-free in the last 16 months, with remarkable changes in his behavior. Conclusions The present case shows that complete radiological resolution of a hypothalamic hamartoma after Gamma-knife technique is unusual but possible, without long-term neurological consequences. Nevertheless, despite its low incidence, if a patient presents neurological symptoms, primarily during the first year after intervention, possible complications of this type of surgery must be taken into account.
Attention deficit / hyperactivity disorder (ADHD) is one of the most prevalent disorders in the child-youth population, with a known impact on learning and school performance. Lack of attention, ...associated executive dysfunction and comorbid problems -particularly those related to learning and anxiety-, strongly determine this conceptual domain. Affected youths have more problems for taking notes, completion of homework, school programming and less motivation to study. Despite greater dedication to homework and greater use of support resources, school failure and nonachievement of curricular objectives are more frequent in these patients. The early diagnosis of ADHD and its comorbidities, the adequate and individualized psychoeducational and pharmacological intervention, have been shown to improve academic prognosis in the short and long term. For this purpose, the active participation of health and education professionals is essential.
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