Spondyloepimetaphyseal dysplasia with neurodegeneration associated with AIFM1 mutation - a novel phenotype of the mitochondrial disease.

In 1999, based on a single family, spondyloepimetaphyseal dysplasia (SEMD) with mental retardation (MR) was described as a novel syndrome with probably X-linked recessive inheritance and unknown molecular defect (MIM 300232). Our purpose was to search for the causative defect in the originally described family and in an independently ascertained second family. All patients had slowly progressive neurodegeneration with central and peripheral involvement and identical skeletal dysplasia. Whole exome sequencing performed in two subjects showed a single plausible candidate - the p.Asp237Gly variant in AIFM1 (chr. Xq26.1). The p.Asp237Gly segregated with disease as indicated by linkage analysis [maximum logarithm of odds score (LOD) score at theta 0 for the two families was 3.359]. This variant had not been previously reported and it was predicted to be pathogenic by Polyphen2, SIFT, MutationTaster and Mutation Assessor. AIFM1 encodes mitochondria associated apoptosis-inducing factor. The AIFM1 gene has been linked with COXPD6 encephalomyopathy (MIM 300816), Cowchock syndrome (MIM 310490) and X-linked deafness with neuropathy (DFNX5, MIM 300614), none of which are similar to SEMD-MR. Our results place SEMD as the third instance of a skeletal phenotype associated with a mitochondrial disease (the others being EVEN-PLUS syndrome caused by mutations of HSPA9 and CODAS syndrome due to LONP1 mutations).

Pelizaeus-Merzbacher disease in patients with molecularly confirmed diagnosis.

Pelizaeus-Merzbacher disease (PMD) is X-linked hypomyelinating leukodystrophy caused by mutations of the PLP1 gene, which codes the proteolipid protein 1. The result of mutations is abnormal myelination - hypomyelination and dysmyelination of cerebral white matter, and in some form of the disease hypomyelinating peripheral neuropathy. DNA samples from 68 patients suspected of PMD due to the clinical course and hypomyelination at magnetic resonance imaging (MRI) were analyzed. Medical history and detailed clinical course of PMD patients were also analyzed. Different mutations of the PLP1 gene were detected in 14 boys from 11 families (~20%). Amongst the molecularly confirmed patients, 13 presented classical PMD forms but clinical phenotypes varied in the severity even amongst siblings. One patient presented a severe connatal form. One mother, obligate carrier, presented complicated SPG2 (spastic paraparesis). There was no phenotype-genotype correlation in our material. In many cases PMD was suspected with a delay of many years, sometimes only after birth of another affected child in the family. Pelizaeus-Merzbacher disease was most frequently misdiagnosed as cerebral palsy.

[Idiopathic absence epilepsy]. / Padaczki idiopatyczne z napadami nieswiadomosci.

UNLABELLED: The International Classification of Epilepsies and Epileptic Syndromes distinguishes four types of idiopathic generalized epilepsies with typical absences: childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME) and epilepsy with generalized grand mal on awakening (EGMA). It is essential in any case when sizures occur to classify the type of epileptic syndrome in order to make prognosis and to choose correct treatment. But it is not always possible to establish diagnosis at the beginning of the disease. Often prolonged observation of the patient and evolution of clinical and EEG features lead to define the epileptic syndrome. The aim of the work was to define the type and frequency of epileptic syndromes and their long-term observation in patients with absences occurred as the first (or the only) type of seizures. SUBJECTS AND METHODS: 31 patients who experienced absences as the first (or the only) type of seizures were selected from the group of 600 subjects suffered from epilepsy admitted to the Neuropediatric Department of the National Research Institute of Mother and Child between 1987 and 1998. Epileptic Syndromes were classified according to the International Classification. RESULTS: There were 31 (5.2%) patients (18 girls and 13 boys) with absences accurred as the first (or the only) type of seizures. The age of the onset of seizures was between 2.5 to 13.5 years (mean 9.3). Seven of them had also tonic-clonic seizures in the course of the observation. They were followed-up for 3 to 9 years (mean 9.2) till the age of 7 to 25 years (mean 18.5). Two epileptic syndromes were established according to the International Classification:--childhood absence epilepsy (CAE) in 27 (4.5%) patients;--juvenile absence epilepsy (JAE) in 4 (0.7%) patients. No one patient showed evolution of disease towards neither juvenile myoclonic epilepsy nor epilepsy with generalized grand mal on awakening during follow-up. CONCLUSIONS: 5.2% of all subjects were patients with idiopathic epilepsies who experienced absences as a first (or the only) type of seizures when absences occur one should consider first of all childhood absence epilepsy and juvenile absence epilepsy. Recognition of juvenile myoclonic epilepsy and epilepsy with generalized grand mal on awakening is less probable.

[Idiopathic headache in children]. / Samoistne bóle glowy u dzieci.

According to literature data, headaches occur in about 40% of preschool children and up to 70% of the children at school age. Most of the headaches, especially in school children, are idiopathic. Symptomatic headaches accompanying a diversity of diseases occur in a small percentage. The idiopathic headaches are the ones in which the pain is not only the main symptom but also the essence of the disease itself. Other idiopathic headaches include: migraine, tension-type headache and Horton headache. The diagnostic and therapeutic problems in idiopathic headaches are discussed.

[Positive effect of falbamate therapy in a boy with refractory epilepsy]. / Pomyslny efekt leczenia preparatem Felbamate u chlopca z oporna na leczenie padaczka.

One of the most important achievement of contemporary epileptology has been a concept of epileptic syndromes. According to the Commission on Classification and Terminology of the International League Against Epilepsy there are many epileptic syndromes which differ from each other not only by prognosis but also by reaction to pharmacotherapy. Nevertheless the differentation between the some of epileptic syndromes may be difficult in spite of quite precise clinical and electrophysiological criteria. Good example of this problem may be the course of disease of the boy who is now eleven years old. His refractory epilepsy which started 7 years ago shares symptoms and signs of both epilepsy with myoclonic-astatic seizures (Doose Syndrome) and Lennox-Gastaut Syndrome. Felbamate therapy was consider to be the turning-point in both therapeutic and diagnostic meaning.

Intractable epilepsy in children who develop epilepsy in the first decade of life--a prospective study.

Prospective studies on 347 children under treatment due to seizures which appeared in the first 10 years of life helped to evaluate and define the incidence of epilepsy resistant to treatment. With regard to each patient the following aspects were analysed: the kind of seizures, their etiology, accompanying neurological disorders and a type of epileptic syndrome, kind of treatment applied before admission to the clinical department as well as socioeconomic conditions of the families. Patients under study were divided into four age groups to evaluate the results. Epilepsy, which was completely resistant to treatment, was observed in 10% of the patients, partially resistant in 20%. Resistance is the outcome of the following factors: onset of epilepsy in early childhood, symptomatic etiology coexisting symptoms of CNS damage, occurrence of unfavourable epileptic syndromes such as Lennox-Gastaut, wrong selection and low dosage of drugs, inappropriate polytherapy and adverse social conditions. On the basis of the results obtained, the authors suggested point evaluation as a kind of screening in prediction of failures in treatment.

Comparison of suspicious and positive colposcopic, cytologic, and histologic findings in the uterine cervix.

One hundred and seven cases of suspicious or positive colposcopic or cytologic findings were histologically analyzed. In cases of colposcopically detectable, atypical changes or suspicious findings as well as of cytologic dysplasias or carcinomas, the histologic diagnoses were almost the same. The results demonstrated that colposcopy and cytology with a quick staining method are of value. Biopsy can quickly follow in cases of suspicious findings.

Intraoperative cytology of tumors.

A quick staining method is described that permits a full cytologic statement on the seriousness of lesions within 3 min intraoperatively. The accuracy of this method of diagnosis and cytodiagnosis of benign and malignant tumors can be compared with histological examinations. The principal advantage is the speed compared with a cytologic fast-cut during operation. Moreover, the preparation or slide is of higher durability; the color and staining response have not faded for 10 yr, so far.

Comparison of suspicious and positive colposcopic, cytologic and histologic findings in the uterine cervix.

One hundred thirty-five cases of suspicious or positive colposcopic or cytologic findings were histologically analyzed. In cases of colposcopically detectable atypical changes or suspicious findings as well as of cytologic dysplasias or carcinomas, the histologic diagnoses were almost the same. The results demonstrated that colposcopy and cytology with a quick staining method are of value. Biopsy can quickly follow in cases of suspicious findings.

[Rapid cytological staining in gynecology]. / Zytologische Schnellfärbung in der gynäkologischen Sprechstunde.

It is reported on a new method of rapid cytological staining permitting valid assessment of pathological changes in the genital area, cytohormonal findings, and criteria of malignancy. The staining technique is simple, inexpensive and quick (2 minutes) and can be performed during daily routine work. The smear can immediately be evaluated and discussed with the patient. For documentation of the results the same criteria apply as in normal cytological diagnosis. Another advantage is the durability of the smears thus permitting later comparison.

[Intraoperative rapid cytological assessment of mammary tumors (author's transl)]. / Intraoperative schnellzytologische Beurteilung von Mammatumoren

A quick staining technique is reported which permits a full cytological statement on the seriousness of mammary tumors within 2 minutes intraoperatively. The accuracy of the method is comparable to that of histological examination. Between 1971 and 1974 a cytological rapid examination was carried out for the assessment of the seriousness of a total of 409 mammary tumors intraoperatively. 71 (equals 17.5 per cent) of the 409 tumors were carcinomas. In 70 of the carcinomas, the severity was confirmed histologically. The method can also be performed in small hospitals which have no pathology laboratory available.