We present a case of megalencephalic leukoencephalopathy with subcortical cysts without macrocephaly and who initially presented with severe psychiatric symptoms. The patient presented with presented with late-onset secondary generalized focal motor seizures, gait ataxia and mild spasticity with hyperreflexia. MRI showed diffuse white matter hyperintensities and bilateral anterotemporal cysts. Genetic analysis confirmed the causal MLC1 mutation and Turner's syndrome. Surprisingly, our patient had no macrocephaly, which is a typical finding in MCL1 mutations; we emphasize that comorbid unrelated Turner's syndrome could explain the absence of macrocephaly: although short stature is typical, microcephaly is not associated with Turner's syndrome. Our observation thus argues for detailed investigations in cases presenting with an atypical clinical picture.

• Klíčová slova
• Depression, Epilepsy, Macrocephaly, Megalencephalic leukoencephalopathy with subcortical cysts, Turner’s syndrome,
• MeSH
• cysty komplikace   diagnostické zobrazování   MeSH
• dědičné demyelinizační nemoci CNS komplikace   diagnostické zobrazování   MeSH
• dospělí MeSH
• lidé MeSH
• megalencefalie * MeSH
• Turnerův syndrom komplikace   diagnostické zobrazování   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

We identified a de novo deletion of 14q11.2 in a Czech patient with developmental delay, mild autistic features, macrosomy, macrocephaly, orthognathic deformities, and dysmorphic facial features. The clinical follow-up of the patient lasting 14 years documented changes in the facial dysmorphism from infancy to adolescence. The deletion affects approximately 200 kb of DNA with five protein-coding genes and two snoRNA genes. Two of the protein-coding genes, SUPT16H and CHD8, have been proposed as candidate genes for a new microdeletion syndrome. Our patient further supports the existence of this syndrome and extends its phenotypic spectrum, especially points to the possibility that orthognathic deformities may be associated with microdeletions of 14q11.2. CHD8 mutations have been found in patients with neurodevelopmental disorders and macrocephaly. The HNRNPC gene, repeatedly deleted in patients with developmental delay, is another candidate as its 5́ end is adjacent to the deletion, and the expression of this gene may be affected by position effect.

• Klíčová slova
• CHD8, Microdeletion 14q11.2, SUPT16H, intellectual disability, macrocephaly, orthognathic deformities,
• MeSH
• chromozomální delece * MeSH
• DNA vazebné proteiny genetika   MeSH
• lidé MeSH
• lidské chromozomy, pár 14 genetika   MeSH
• megalencefalie diagnóza   genetika   MeSH
• mentální retardace diagnóza   genetika   MeSH
• mladiství MeSH
• mnohočetné abnormality diagnóza   genetika   MeSH
• následné studie MeSH
• transkripční faktory genetika   MeSH
• vývojové poruchy u dětí diagnóza   genetika   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CHD8 protein, human MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• transkripční faktory MeSH

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

• MeSH
• lidé MeSH
• syndrom mnohočetného hamartomu diagnóza   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• fosfohydroláza PTEN genetika   MeSH
• fotografování MeSH
• lidé MeSH
• mutace * MeSH
• syndrom mnohočetného hamartomu genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• fosfohydroláza PTEN MeSH
• PTEN protein, human MeSH Prohlížeč

Cowden syndrome is an inherited disease characterized by mucocutaneous lesions, gastrointestinal hamartomatous polyposis and an increased risk of breast, thyroid and endometrial carcinomas. Despite well described phenotypic expression of this disease, it is not easy to determine correct clinical diagnosis. In this case report we present a clinical history of a patient with Cowden syndrome. When he was 22 years old, he was found to have polyposis of gastrointestinal tract. The diagnosis of Peutz-Jeghers syndrome was established. Owing to intensive belly spasms, as a 36-year-old he was sent to another gastroenterological department where the thorough gastrointestinal tract examination was performed. We found glycogenic acanthosis of the esophagus; diffuse polyposis with large polyps within the stomach, and polyposis with small polyps in duodenum, colon, and rectum. We also noted the presence of excessive mucocutaneous papillomatosis of the lips and subtle skin lesions. Possible Cowden syndrome diagnosis was suggested. The same year he underwent plastic operation of the lips. During surgery, diffuse nodularity of the trachea was also noted. After plastic operation and assessment of Cowden syndrome as a possible diagnosis, he was recommended for a genetic examination. Diagnosis of Cowden syndrome was confirmed by sequencing analysis of the PTEN gene (phosphatase and tensin homolog deleted on chromosome 10). We found 'c.825_840delAAATACATTCTTCATA' deletion. This case affirmed that, for establishment of a correct diagnosis, especially for rare clinically overlapping syndromes, molecular testing is usually the only reliable method.

• MeSH
• delece genu * MeSH
• dospělí MeSH
• fosfohydroláza PTEN genetika   MeSH
• kůže patologie   MeSH
• lidé MeSH
• nádory rtu komplikace   genetika   patologie   MeSH
• papilom komplikace   genetika   patologie   MeSH
• střevní polypóza komplikace   genetika   patologie   MeSH
• syndrom mnohočetného hamartomu komplikace   genetika   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfohydroláza PTEN MeSH

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent skin cancer worldwide, however, its metastatic spreading is extremely rare. CASE: We present a case of advanced BCC with rapid growth of new tumor lesions in a patient who was later diagnosed with Gorlin syndrome. Due to the advanced disease stage, the patient was examined for circulating tumor cells (CTCs), which are used as a prognostic marker in some metastatic malignancies. To date, no studies have been found that could assess the BCC tumor and the presence of CTCs in peripheral blood. CTCs were obtained after each surgical excision and during systemic oncological therapy from the peripheral venous blood by size-based isolation method (Metacell®) and cultured in vitro for 7 days. CTCs were enriched by size-based separation and examined using vital fluorescence microscopy. Cytomorphological comparison of CTCs with cells from the tumor lesions was provided. In the course of the treatment, the CTCs count in the blood decreased after surgical removal of the tumorous mass, but finally, the sustained and persisting decrease in CTCs was achieved with a hedgehog pathway inhibitor treatment. CONCLUSION: The detection of CTCs points a systematic disease behavior in this case.

• Klíčová slova
• BCC, CTCs, basal cell carcinoma, circulating tumor cells, hedgehog pathway inhibitor,
• MeSH
• bazocelulární karcinom * MeSH
• lidé MeSH
• nádorové cirkulující buňky * MeSH
• počet buněk MeSH
• proteiny hedgehog MeSH
• syndrom mnohočetného hamartomu * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• proteiny hedgehog MeSH

BACKGROUNDS: Cowden syndrome (CS) is a rare autosomal dominant disorder with an increased risk of breast, thyroid and uterine cancer development. The International Cowden Consortium has defined strict diagnostic criteria for individuals and families suspected of having CS. PATIENTS AND METHODS: We analyzed the genomic DNA of 16 patients by sequencing analysis and MLPA (multiplex ligation-dependent probe amplification) method. RESULTS: We found germline mutations, c.825_840del, resp. c.438delT, in 2 patients. Both patients fulfilled strict diagnostic criteria. The other patients, except one, who did not fulfil the criteria, did not harbour any pathogenic mutation. Patients not fulfilling strict diagnostic criteria were included in the study according to major CS criteria but not pathogenic. CONCLUSION: Our results and information from relevant articles show that strict international criteria are well established and analysis of "CS-like" patients has no significant prognostic meaning.

• MeSH
• dospělí MeSH
• fosfohydroláza PTEN genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• sekvenční analýza DNA MeSH
• syndrom mnohočetného hamartomu diagnóza   genetika   patologie   MeSH
• techniky amplifikace nukleových kyselin MeSH
• zárodečné mutace * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• fosfohydroláza PTEN MeSH

BACKGROUND: Cowden syndrome (CS) is a cancer predisposition syndrome associated with increased risk of breast, thyroid, and endometrial cancers, and is characterized by development of benign mucocutaneous lesions. CASE PRESENTATION: Here we report on a 58-year-old woman with multiple primary malignancies and subtle mucocutaneous lesions such as small polyps and wart-like papulas. Over a period of 23 years, she developed various malignant neoplasms including thyroid, ovarian, stomach, and colon carcinomas, and a benign meningioma. Direct sequencing analysis of the PTEN gene revealed a novel germline mutation (c.438delT, p.Leu146X). CONCLUSION: This case demonstrates that Cowden syndrome is a multi-system disease that can result in the development of multiple malignant and benign tumors.

• MeSH
• fatální výsledek MeSH
• fosfohydroláza PTEN genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• meningeální nádory genetika   MeSH
• meningeom genetika   MeSH
• mnohočetné primární nádory genetika   MeSH
• nádory štítné žlázy genetika   MeSH
• nádory tračníku genetika   MeSH
• nádory vaječníků genetika   MeSH
• nádory žaludku genetika   MeSH
• nesmyslný kodon MeSH
• posunová mutace MeSH
• sekvenční delece MeSH
• syndrom mnohočetného hamartomu genetika   patologie   MeSH
• zárodečné mutace * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfohydroláza PTEN MeSH
• nesmyslný kodon MeSH
• PTEN protein, human MeSH Prohlížeč

Maternal immune activation (MIA) during pregnancy represents an important environmental factor in the etiology of schizophrenia and autism spectrum disorders (ASD). Our goal was to investigate the impacts of MIA on the brain and behavior of adolescent and adult offspring, as a rat model of these neurodevelopmental disorders. We injected bacterial lipopolysaccharide (LPS, 1 mg/kg) to pregnant Wistar dams from gestational day 7, every other day, up to delivery. Behavior of the offspring was examined in a comprehensive battery of tasks at postnatal days P45 and P90. Several brain parameters were analyzed at P28. The results showed that prenatal immune activation caused social and communication impairments in the adult offspring of both sexes; males were affected already in adolescence. MIA also caused prepulse inhibition deficit in females and increased the startle reaction in males. Anxiety and hypolocomotion were apparent in LPS-affected males and females. In the 28-day-old LPS offspring, we found enlargement of the brain and decreased numbers of parvalbumin-positive interneurons in the frontal cortex in both sexes. To conclude, our data indicate that sex of the offspring plays a crucial role in the development of the MIA-induced behavioral alterations, whereas changes in the brain apparent in young animals are sex-independent.

• Klíčová slova
• autism, chronic bacterial infection, development, lipopolysaccharide, macrocephaly, maternal immune activation, parvalbumin-positive interneurons, prenatal infection, schizophrenia, sex differences,
• MeSH
• chování zvířat * MeSH
• imunohistochemie MeSH
• imunomodulace * MeSH
• interneurony metabolismus   MeSH
• krysa rodu Rattus MeSH
• lipopolysacharidy imunologie   MeSH
• matka - expozice noxám MeSH
• mikroglie imunologie   metabolismus   MeSH
• mozek imunologie   metabolismus   MeSH
• parvalbuminy metabolismus   MeSH
• sexuální faktory MeSH
• sociální chování MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lipopolysacharidy MeSH
• parvalbuminy MeSH