Maternal mosaicism underlies the inheritance of a rare germline AKT3 variant which is responsible for megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome in two Roma half-siblings.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a developmental brain disorder characterized by an enlarged brain size with bilateral perisylvian polymicrogyria and a variable degree of ventriculomegaly. MPPH syndrome is associated with oromotor dysfunction, epilepsy, intellectual disability and postaxial hexadactyly. The molecular diagnosis of this disorder is established by the identification of a pathogenic variant in either AKT3, CCND2 or PIK3R2.

[DISEASE BURDEN OP DUCHENNE MUSCULAR DYSTROPHY PATIENTS AND THEIR CAREGIVERS].

Background And Purpose: Data on the disease burden of Duchenne Muscular Dystrophy are scarce in Hungary. The aim of this study was to assess patients' and their caregivers' health related quality of life and healthcare utilisations.

Methods: A cross sectional survey was performed as part of the European BURQOL-RD project.

[FINANCING OF MEDICINES FOR TREATMENT OF RARE DISEASES OF THE NERVOUS SYSTEM. ORPHAN DRUGS IN RARE NEUROLOGICAL DISEASES].

Objectives: Nervous system involvement is expected up to 60-70% in case of rare diseases. This article aims to present the financial methods and expenditures of rare neurological diseases' orphan medicinal products being financed in the frame of Hungarian social insurance system in 2012.

Methods: The subsidized orphan medicines were selected on the Orphanet portal 2012 while orphans financed by compessionate use were provided by the Hungarian National Insurance Fund Administration (OEP) database.

Kleefstra syndrome in Hungarian patients: additional symptoms besides the classic phenotype.

Background: Kleefstra syndrome is a rare genetic disorder, with core phenotypic features encompassing developmental delay/intellectual disability, characteristic facial features - brachy(micro)cephaly, unusual shaped eyebrows, flat face with hypertelorism, short nose with anteverted nostrils, thickened lower lip, carpmouth with macroglossia - and childhood hypotonia. Some additional symptoms are observed in different percentage of the patients. Epilepsy is common symptom as well.

Phenotypic variability in a Hungarian patient with the 4q21 microdeletion syndrome.

Background: Interstitial deletions of 4q21 (MIM 613509) have already been reported in more than a dozen patients with deletions ranging from 2 to 15.1 Mb delineating a common phenotype including marked growth restriction, hypotonia, severe developmental delay with absent or delayed speech and distinctive facial features. A minimal critical region of 1.

It is time to take timing seriously in clinical genetics.

Observations made by molecular techniques on the genome along the individuals' lifetime indicate that the genome in somatic cells displays changes at molecular, cellular, and organismal levels. Timing of genetic events leading to somatic mosaicism and gene expression dynamism results in a highly important variable for comprehending the role of genetics in health and disease. Consideration of time in clinical genetics should be enthusiastically invested into research strategy, interpretation of the results, diagnostic routine, and particularly in ethical discussions.

Partial trisomy of the pericentromeric region of chromosome 5 in a girl with binder phenotype.

The patient reported here displayed most characteristic features of Binder syndrome (OMIM: 155050), a rare maxillonasal malformation with unknown etiology. She was sent for genetic evaluation at the age of 10 years because of facial dysmorphism and borderline intellectual disability. Cytogenetic analyses showed a de novo supernumerary small ring chromosome with a pericentromeric region of chromosome 5 in all lymphocytes.

[Shift of focus in the financing of Hungarian drugs. Reimbursement for orphan drugs for treating rare diseases: financing of enzyme replacement therapy in Hungary].

Focusing on the benefits of patients with rare disease the authors analysed the aspects of orphan medicines financed in the frame of the Hungarian social insurance system in 2012 in order to make the consumption more rational, transparent and predictable. Most of the orphan drugs were financed in the frame of compassionate use by the reimbursement system. Consequently, a great deal of crucial problems occurred in relation to the unconventional subsidized method, especially in the case of the highest cost enzyme replacement therapies.

[Cystic fibrosis -- disease burden and health-related quality of life of patients and their caregivers: results of the European BURQOL-RD survey in Hungary].

Introduction: Data on disease burden of cystic fibrosis in Hungary are scarce.

Aim: To assess quality of life and resource utilisations of patients with cystic fibrosis.

Method: In a cross-sectional survey (BURQOL-RD project), the EQ-5D-5L questionnaire was applied and healthcare utilisations were retrospectively surveyed.

Deletion of 4q28.3-31.23 in the background of multiple malformations with pulmonary hypertension.

The 4q deletion syndrome shows a broad spectrum of clinical manifestations consisting of key features comprising growth failure, developmental delay, craniofacial dysmorphism, digital anomalies, and cardiac and skeletal defects. We have identified a de novo interstitial distal deletion in a 9 month-old girl with growth failure, developmental delay, ventricular septum defect in the subaortic region, patent foramen ovale and patent ductus arteriosus, vascular malformation of the lung, dysgenesis of the corpus callosum and craniofacial dysmorphism using array-comparative genomic hybridization. This de novo deletion is located at 4q28.

[Identifying rare genomic disorders with array comparative genomic hybridization in Hungary].

Introduction: In the past decade the study of genomic disorders has received more interest. Array comparative genome hybridization is a widely spread diagnostic method in the research of genomic disorders. This method was implemented in the laboratory of the authors in 2012.

[Hungarian national plan and strategy for rare diseases].

The rarity of low prevalence diseases and the lack of information, research, diagnosis, treatment and expert availability may mean that the people affected do not benefit from the health resources and services they need. Rare diseases are considered to have little impact on society as a whole, yet they pose serious difficulties for sufferers and their families. By the end of the last century, two robust achievements in science and technology, i.

[Diagnostic delay of rare diseases in Europe and in Hungary].

Unlabelled: The long diagnostic delay is a characteristic problem of rare disease patients.

Aims: Diagnostic delay was studied in 14 countries by EurordisCare2 involving patient organizations.

Methods: 252 Hungarian patients (cystic fibrosis; Duchenne muscular dystrophy; tuberous sclerosis, retinitis pigmentosa, and Williams' syndrome) completed the questionnaires.

Jumping translocation of 15q24-qter resulting in partial trisomy: a case report.

We report on a jumping translocation with five different cell lines detected in four tissues in a 2-year-old patient. This rare type of chromosomal abnormality (not more than 30 cases published so far) proved to be a series of non-reciprocal translocations of the 15q24-qter donor chromosome segment to the telomeric region of chromosomes 5q, 10q, 16q and 19p, respectively. The process, in addition to a few cells without translocation, resulted in partial trisomy of 15q24-qter which was associated with somatic overdevelopment in the patient, with hemihypertrophy and minor anomalies.

Hypothesis: epigenetic effects will require a review of the genetics of child development.

The worldwide prevalence of developmental disorders in children including birth defects, mental dysfunctions, as well as early-life abnormalities leading to the predisposition for adult diseases is one of the major unsolved problems in medicine and societies. Child development is influenced by both genes and the environment; however, the role of the environment is more emphatic, since the genome is most vulnerable to environmental factors during early development due to the high cellular differentiation rate. This inherent characteristic of child development lays the stress on a probabilistic rather than a deterministic view with regard to the manifestation of developmental disorders.

Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations.

Rett syndrome (RTT) is characterized by a relatively specific clinical phenotype. We screened 152 individuals with RTT phenotype. A total of 22 different known MECP2 mutations were identified in 42 subjects (27.

[First decade of post-genomic era. Hopes, disappointments, new answers].

The first decade after the announcement of the draft sequence of human genome has brought spectacular advances in basic science, however, the fact that human health did not benefit that much caused disappointment, as well. In order to explore the causes of the absence of revolution in medicine, beside the extension of research strategy new conception about the role of genetics in health and disease should also be considered. In order to resolve the disappointments, the author recommends a new perspective to view the role of genetics in health and diseases.

The medical geneticist as expert in the transgenerational and developmental aspects of diseases.

The increased knowledge of genetics has raised new questions, and confusion has been growing about the evaluation of the results of recent research and the role of geneticists in the genomic medicine. If we focus on transgenerational and developmental aspects of diseases, the answers might be more evident.

The genetics and clinical characteristics of constitutional ring chromosomes.

Constitutional ring chromosomes are generally believed to be the result of de novo breakage of both end-segments of a chromosome during meiosis or early postzygotic mitosis, with the ends joining to give a continuous ring. This mechanism presumes the loss of some genetic material during ring formation. Ring chromosomes thus represent deletions of genetic material.

[Clinical classification of congenital limb abnormalities].

Limb developmental defects are well-known, conspicuous abnormalities. Until this day, the background has still not been completely revealed, however, the development of scientific methods provides more and more opportunities which may help to understand developmental processes and defects of this compound system. Considering these aspects, following data collection from patients with limb developmental defects, we began a study with the purpose of finding/establishing a classification system that is suitable for morphological and clinical distinctions, besides considering developmental aspects, and may help to indicate adequate genetic examinations.

Phenotypic variants of the deafness-associated mitochondrial DNA A7445G mutation.

A number of nuclear and mitochondrial mutations have been implicated in non-syndromic hearing loss. Among them, various mutations of mitochondrial Ser(UCN)-tRNA and 12S rRNA genes have been found to be associated with deafness; the A7445G mitochondrial DNA (mtDNA) in this group is unique, simultaneously affecting two different mitochondrial genes, encoding the Ser(UCN)-tRNA and the first subunit of cytochrome oxidase. Besides the hearing loss, it is mainly associated with palmoplantar keratoderma, though; different phenotypic associations have been reported.

[Psychological aspects of presymptomatic diagnosis in Huntington disease].

Introduction: Huntington disease is an autosomal dominant, progressive neurodegenerative disorder, starting in adulthood. International recommendations were created for presymptomatic testing (genetic test performed before symptoms appear). During the initial preparation for presymptomatic testing, a genetic counsellor, neurologist and psychologist attend.