Spectrum of neurodevelopmental disabilities: a cohort study in hungary.

The spectrum of neurodevelopmental disabilities was studied in a cohort of patients in Hungary. A search for etiologies and assessment of the degree of intellectual disability were carried out. The study included 241 (131 boys) patients. Disability occurred without any prenatal, perinatal, and/or neonatal adverse events in 167 patients. They were classified into the following subgroups: genetic syndromes with recognized etiology, global developmental delay/intellectual disability in association with dysmorphic features but unknown etiology, global developmental delay/intellectual disability without dysmorphic features and recognized etiology, brain malformations, inborn errors of metabolism, leukoencephalopathies, epileptic syndromes, developmental language impairment, and neuromuscular disorders. Adverse events occurred in 74 children classified into subgroups such as cerebral palsy after delivery preterm or at term, and disabilities without cerebral palsy. The etiology was identified in 66.4%, and genetic diagnosis was found in 19.5%. Classification of neurodevelopmental disorders contribute to etiological diagnosis, proper rehabilitation, and genetic counseling.

Nemaline myopathy type 2 (NEM2): two novel mutations in the nebulin (NEB) gene.

Nemaline myopathy is a type of the heterogeneous group of congenital myopathies. Generalized hypotonia, weakness, and delayed motor development are the main clinical features of the typical congenital form. Histopathology shows characteristic nemaline rods in the muscle biopsy. Mutations in at least 7 genes, including nebulin gene (NEB), proved to be responsible for this muscle disease. We present a boy with nemaline myopathy type 2 (NEM2) caused by compound heterozygosity for 2 novel mutations, a deletion and a duplication in the NEB gene. The deletion was inherited from the father and the duplication from the mother. Testing all family members supports genetic counseling.

Early detection of Angelman syndrome resulting from de novo paternal isodisomic 15q UPD and review of comparable cases.

BACKGROUND: Angelman syndrome is a rare neurogenetic disorder that results in intellectual and developmental disturbances, seizures, jerky movements and frequent smiling. Angelman syndrome is caused by two genetic disturbances: either genes on the maternally inherited chromosome 15 are deleted or inactivated or two paternal copies of the corresponding genes are inherited (paternal uniparental disomy). A 16-month-old child was referred with minor facial anomalies, neurodevelopmental delay and speech impairment. The clinical symptoms suggested angelman syndrome. The aim of our study was to elucidate the genetic background of this case. RESULTS: This study reports the earliest diagnosed angelman syndrome in a 16-month-old Hungarian child. Cytogenetic results suggested a de novo Robertsonian-like translocation involving both q arms of chromosome 15: 45,XY,der(15;15)(q10;q10). Molecular genetic studies with polymorphic short tandem repeat markers of the fibrillin-1 gene, located in the 15q21.1, revealed that both arms of the translocated chromosome were derived from a single paternal chromosome 15 (isodisomy) and led to the diagnosis of angelman syndrome caused by paternal uniparental disomy. CONCLUSIONS: AS resulting from paternal uniparental disomy caused by de novo balanced translocation t(15q;15q) of a single paternal chromosome has been reported by other groups. This paper reviews 19 previously published comparable cases of the literature. Our paper contributes to the deeper understanding of the phenotype-genotype correlation in angelman syndrome for non-deletion subclasses and suggests that patients with uniparental disomy have milder symptoms and higher BMI than the ones with other underlying genetic abnormalities.

Congenital myasthenic syndromes and transient myasthenia gravis.

Hypotonia in the neonatal period and early infancy is a common clinical finding. It can be caused by various heterogeneous disorders of different origin which might lead to diagnostic difficulties. Disorders of the neuromuscular junction, such as congenital myasthenic syndromes and neonatal transient myasthenia gravis are among the aetiologies. We report on a case of congenital myasthenia caused by mutation in the long cytoplasmic loop of the epsilon subunit of the acetylcholine receptor and a neonate of a myasthenic mother diagnosed with transient myasthenia gravis.

Birth prevalence of neural tube defects: a population-based study in South-Eastern Hungary.

PURPOSE: Primary prevention by periconceptional folic acid supplementation can significantly reduce the risk of neural tube defects. EUROCAT, the European network of population-based registries for the epidemiologic surveillance of congenital anomalies, lacks sufficient data on the birth prevalence of neural tube defects in Hungary before and after the promotion of primary prevention by folic acid. Our aims were to compare the birth prevalence of neural tube defects (myelomeningocele, anencephaly and encephalocele) over two 12-year periods in South-Eastern Hungary. Further aims were to compare our data to those ones in other areas in Europe. METHODS: Data were collected from the databases of the Department of Hungarian Congenital Abnormality Registry. The total and live birth prevalence rate of neural tube defects were calculated and compared over 1980-1991 and 1994-2005. In addition, the trends in the total birth prevalence, the number of live births and terminations for and stillbirths with neural tube defects were analysed throughout the period of 1994-2005. RESULTS: A significant decline was found in the total and live birth prevalence of myelomeningocele, anencephaly and encephalocele over 1994-2005 compared to the period of 1980-1991. The total birth prevalence of neural tube defects, however, showed a trend of increase after 1994, with declining number of live births and increasing number of terminations for neural tube defects. CONCLUSION: Public health measures are warranted in order to replace termination of pregnancy with primary prevention in South-Eastern Hungary.

Lissencephaly and band heterotopia: LIS1, TUBA1A, and DCX mutations in Hungary.

The spectrum of lissencephaly ranges from absent (agyria) or decreased (pachygyria) convolutions to less severe malformation known as subcortical band heterotopia. Mutations involving LIS1 and TUBA1A result in the classic form of lissencephaly, whereas mutations of the DCX gene cause lissencephaly in males and subcortical band heterotopia in females. This report describes the clinical manifestations and imaging and genetic findings in 2 boys with lissencephaly and a girl with subcortical band heterotopia. An ovel mutation (c.83_84delAT, p.Tyr28Phefs*31) was identified in LIS1 in 1 of the boys with lissencephaly and another novel mutation (c.200delG, p.Ile68Leufs*87) was found in DCX in the girl with subcortical band heterotopia. The mutations appeared in the first half of the genes and are predicted to result in truncated proteins. A mutation was found in the TUBA1A gene (c.1205G>A, p.Arg402His) in the other boy. This mutation affects the folding of tubulin heterodimers, changing the interactions with proteins that bind microtubules.

Corpus callosum anomalies: birth prevalence and clinical spectrum in Hungary.

Data regarding the epidemiology of callosal anomalies are contradictory. We performed a population-based retrospective survey to study the birth prevalence and clinical features of agenesis/hypoplasia of the corpus callosum and accompanying central nervous system and somatic abnormalities in southeastern Hungary between July 1, 1992 and June 30, 2006. Among 185,486 live births, 38 patients (26 boys and 12 girls) manifested agenesis/hypoplasia of the corpus callosum, corresponding to a prevalence of 2.05 per 10,000 live births (95% confidence interval, 1.4-2.7). Callosal anomalies were isolated in 18 patients, and were associated with other central nervous system malformations in five children. Both central nervous system and noncentral nervous system abnormalities were evident in seven patients, whereas callosal dysgenesis was accompanied only by somatic anomalies in eight children. Five of 18 patients with isolated agenesis/hypoplasia of the corpus callosum remained asymptomatic. Developmental delay, intellectual disability, or epilepsy occurred in all patients, except one, when callosal anomalies were combined with other brain or somatic abnormalities. Five patients with multiplex malformations died. Callosal anomalies form a clinically significant and relatively frequent group of central nervous system malformations.

Holoprosencephaly in hungary: birth prevalence and clinical spectrum.

A retrospective population based survey of patients born with holoprosencephaly in South-Eastern Hungary between July 1, 1992 and June 30, 2006 was performed. All live birth cases with craniofacial and non-craniofacial abnormalities were included in the study. A total of 9 patients (5 boys and 4 girls) were found with holoprosencephaly among 185 486 live births, which correspond to a birth prevalence of 0.49 per 10,000 live births (95% confidence interval [CI]: 0.17-0.80). These figures were similar to those ones found in New York State and several European regions. In our series one newborn had trisomy 13. Eight patients did not have chromosomal abnormalities on routine testing, 4 of them had craniofacial abnormalities only and another 4 showed non-craniofacial anomalies as well. Three patients died in the neonatal period and another one in childhood. Patients surviving the neonatal period had intellectual and motor handicap, and epilepsy.