BACKGROUND: Autism spectrum disorders (ASD) and intellectual disabilities (ID) are heterogeneous and complex developmental diseases with significant genetic backgrounds and overlaps of genetic susceptibility loci. Copy number variants (CNVs) are known to be frequent causes of these impairments. However, the clinical heterogeneity of both disorders causes the diagnostic efficacy of CNV analysis to be modest. This could be resolved by stratifying patients according to their clinical features. AIM: First, we sought to assess the significance of particular clinical features for the detection of pathogenic CNVs in separate groups of ID and ASD patients and determine whether and how these groups differ from each other in the significance of these variables. Second, we aimed to create a statistical model showing how particular clinical features affect the probability of pathogenic CNV findings. METHOD: We tested a cohort of 204 patients with ID (N = 90) and ASD (N = 114) for the presence of pathogenic CNVs. We stratified both groups according to their clinical features. Fisher's exact test was used to determine the significance of these variables for pathogenic CNV findings. Logistic regression was used to create a statistical model of pathogenic CNV findings. RESULTS: The frequency of pathogenic CNV was significantly higher in the ID group than in the ASD group: 18 (19.78%) versus 8 (7%) (p < 0.004). Microcephaly showed a significant association with pathogenic findings in ID patients (p < 0.01) according to Fisher's exact test, whereas epilepsy showed a significant association with pathogenic findings in ASD patients (p < 0.01). The probability of pathogenic CNV findings when epilepsy occurred in ASD patients was more than two times higher than if epilepsy co-occurred with ID (29.6%/14.0%). Facial dysmorphism was a significant variable for detecting pathogenic CNVs in both groups (ID p = 0.05, ASD p = 0.01). However, dysmorphism increased the probability of pathogenic CNV detection in the ID group nearly twofold compared to the ASD group (44.4%/23.7%). The presence of macrocephaly in the ASD group showed a 25% probability of pathogenic CNV findings by logistic regression, but this was insignificant according to Fisher's exact test. The probability of detecting pathogenic CNVs decreases up to 1% in the absence of dysmorphism, macrocephaly, and epilepsy in the ASD group. CONCLUSION: Dysmorphism, microcephaly, and epilepsy increase the probability of pathogenic CNV findings in ID and ASD patients. The significance of each feature as a predictor for pathogenic CNV detection differs depending on whether the patient has only ASD or ID. The probability of pathogenic CNV findings without dysmorphism, macrocephaly, or epilepsy in ASD patients is low. Therefore the efficacy of CNV analysis is limited in these patients.

• Klíčová slova
• ADHD, Autism spectrum disorders, CNV, Congenital malformations, Epilepsy, Facial dysmorphia, Growth defects, Intellectual disabilities, Macrocephaly, Microcephaly,
• Publikační typ
• časopisecké články MeSH

The authors present the ocular finding in a patient sent to the Department of Paediatric Ophthalmology at the Children's University Hospital - Faculty of Medicine, Comenius University in Bratislava at the age of 3 months, with congenital glaucoma in her right eye and bilateral high myopia. The family anamnesis of the patient shows repeated occurrence of stunted growth, myopia, facial dysmorphia and cataract. The child's mother had high myopia, the mother's brother underwent cataract surgery, the child's grandmother and her sisters and the child's great grandmother had high myopia and glaucoma, and probably underwent cataract surgery at a young age. The child's mother and grandmother underwent a genetic examination, with a conclusion of Marshall syndrome. Within the framework of neonatal screening, poor cortical auditory evoked potential, a defect of the interventricular septum and bifid uvula were diagnosed in the child. With regard to the overall finding in the patient and the genetic family history, we suspected Marshall syndrome. A genetic examination determined Stickler syndrome type 1 with the presence of mutation in the COL2A gene (variant c.2710C >T (p.Arg904Cys,rs121912882)). Due to high intraocular pressure with the impossibility of compensation by medication, bilateral trabuculectomy was performed on the patient. At present the patient has intraocular pressure compensated with adjuvant medicamentous therapy. With regard to high myopia and pronounced degenerative changes on the periphery of the retina in the sense of lattice degeneration, preventive cryopexy of the retinal periphery is planned. A molecular genetic analysis helped diagnose the pathology as Stickler syndrome type 1, which manifested phenotype symptoms of Marshall syndrome or Stickler syndrome type 2. Key words: Marshall syndrome, Stickler syndrome, mid-facial dysmorfism, myopia, glaucoma, cataract.

• Klíčová slova
• Marshall syndrome, Stickler syndrome, cataract, glaucoma, mid-facial dysmorfism, myopia,
• MeSH
• artritida * diagnóza   genetika   MeSH
• kojenec MeSH
• lidé MeSH
• myopie MeSH
• nemoci pojiva * diagnóza   genetika   MeSH
• odchlípení sítnice * diagnóza   genetika   MeSH
• percepční nedoslýchavost * diagnóza   genetika   MeSH
• rodokmen MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The authors describe a case of 22 years old adult male with Mulibrey syndrome. This is an autosomal recessive hereditary disease that manifests through multiple malformations. Diagnosis of Mulibrey syndrome in the present case was first based on clinical signs (facial dysmorphia, growth disorder, muscle hypotrophy) and was later confirmed by genetic examination. At the age of 18 months, the patient underwent surgery for Wilms' tumour followed by cytostatic therapy. Facial, neck and lower extremities oedemas started to occur from the age of 11 years when diastolic ventricular dysfunction was also diagnosed. Pericardiectomy was performed at the age of 13 with no significant clinical effect. Significant ascites dominated the clinical picture and required repeated paracentesis at the age of 15 years. Subjective complaints improved when adequate diuretic therapy was introduced and ascites was managed with conservative therapy without the need for further paracentesis.

• MeSH
• ascites komplikace   terapie   MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• syndrom Mulibrey komplikace   diagnóza   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH