[Autism spectrum disorders - epidemiology, symptoms, comorbidity and diagnosis]. / Zaburzenia ze spektrum autyzmu - epidemiologia, objawy, wspólzachorowalnosc i rozpoznawanie.

In the new classification of American Psychiatric Association - DSM-5 - a category of autistic spectrum disorders (ASD) was introduced, which replaced autistic disorder, Asperger syndrome, childhood disintegrative disorder and pervasive developmental disorder not otherwise specified. ASD are defined by two basic psychopathological dimensions: communication disturbances and stereotyped behaviors, and the diagnosis is complemented with the assessment of language development and intellectual level. In successive epidemiological studies conducted in 21 century the prevalence of ASD has been rising, and currently is estimated at 1% in general population. The lifetime psychiatric comorbidity is observed in majority of patients. The most common coexisting diagnoses comprise disorders ofanxiety-affective spectrum, and in about 1/3 of patients attention deficit/ hyperactivity disorders could be diagnosed. Prodromal symptoms of ASD may emerge before 12 months of life, however reliability of diagnosis at such an early age is poor. Several screening instruments, based on the parental and/or healthcare professional assessments may be helpful in ASD detection. However, structured interviews and observation schedules remain the gold standard of diagnosis.

Clinical and molecular characteristics of Kabuki syndrome patients with missense variants-novel features and literature review.

Kabuki Syndrome (KS) encompasses a spectrum of clinical manifestations, primarily attributed to pathogenic variants in the KMT2D gene. This study aims to elucidate novel features in KS patients with missense variants, contrasting their presentation with both literature-reported cases of patients with missense pathogenic variants as well as other KS patients with truncating pathogenic variants. Employing a survey questionnaire and clinical evaluations, we examined ten KS patients with missense variants, focusing on their dysmorphism characteristics, behavior and psychomotor development. We identified unique features in missense variant patients, including foot hyperesthesia, musicality, and sensory integration disorders. Notably, despite similarities in developmental trajectories, distinct phenotypic traits emerged in missense variant cases, suggesting a potential genotype-phenotype correlation. These findings contribute to a deeper understanding of KS heterogeneity and underscore the importance of genotype-specific characterization for prognostic and therapeutic considerations. Further exploration of genotype-phenotype relationships promises to refine clinical management strategies and enhance patient outcomes in this complex syndrome.

Application of array comparative genomic hybridization in 102 patients with epilepsy and additional neurodevelopmental disorders.

Copy-number variants (CNVs) collectively represent an important cause of neurodevelopmental disorders such as developmental delay (DD)/intellectual disability (ID), autism, and epilepsy. In contrast to DD/ID, for which the application of microarray techniques enables detection of pathogenic CNVs in -10-20% of patients, there are only few studies of the role of CNVs in epilepsy and genetic etiology in the vast majority of cases remains unknown. We have applied whole-genome exon-targeted oligonucleotide array comparative genomic hybridization (array CGH) to a cohort of 102 patients with various types of epilepsy with or without additional neurodevelopmental abnormalities. Chromosomal microarray analysis revealed 24 non-polymorphic CNVs in 23 patients, among which 10 CNVs are known to be clinically relevant. Two rare deletions in 2q24.1q24.3, including KCNJ3 and 9q21.13 are novel pathogenic genetic loci and 12 CNVs are of unknown clinical significance. Our results further support the notion that rare CNVs can cause different types of epilepsy, emphasize the efficiency of detecting novel candidate genes by whole-genome array CGH, and suggest that the clinical application of array CGH should be extended to patients with unexplained epilepsies.

The role of genetic factors and pre- and perinatal influences in the etiology of autism spectrum disorders - indications for genetic referral. / Znaczenie czynników genetycznych oraz przed- i okoloporodowych w etiologii zaburzen ze spektrum autyzmu - wskazania do konsultacji genetycznej.

Autism spectrum disorders (ASD) are caused by disruptions in early stages of central nervous system development and are usually diagnosed in first years of life. Despite common features such as impairment of socio-communicative development and stereotypical behaviours, ASD are characterised by heterogeneous course and clinical picture. The most important aetiological factors comprise genetic and environmental influences acting at prenatal, perinatal and neonatal period. The role of rare variants with large effect i.e. copy number variants in genes regulating synapse formation and intrasynaptic connections is emphasised. Common variants with small effect may also be involved, i.e. polymorphisms in genes encoding prosocial peptides system - oxytocin and vasopressin. The environmental factors may include harmful effects acting during pregnancy and labour, however their specificity until now is not confirmed, and in some of them a primary genetic origin cannot be excluded. In several instances, especially with comorbid disorders - intellectual disability, epilepsy and dysmorphias - a detailed molecular diagnostics is warranted, which currently may elucidate the genetic background of disorder in about 20% of cases.