Recessive Mutations in POLR3B Encoding RNA Polymerase III Subunit Causing Diffuse Hypomyelination in Patients with 4H Leukodystrophy with Polymicrogyria and Cataracts.

The diagnosis of 4H leukodystrophy (hypomyelination, hypogonadotropic hypogonadism, and hypodontia) is based on clinical findings and magnetic resonance imaging (MRI). Recently, mutations of the genes encoding Pol III (RNA polymerase III) subunit A (POLR3A) and subunit B (POL3B) have been identified as the genetic causes of hypomyelination. We describe two Polish female siblings aged 5 and 10 years with compound heterozygous mutations in POLR3B. They both presented with similar clinical symptoms and MRI findings presenting as 4H leukodystrophy, and the association of polymicrogyria and cataract. According to our observation in young children with the absence of hypogonadotropic hypogonadism, brain MRI pattern is very essential in proper early diagnosis of 4H leukodystrophy. All clinical and radiological results are of course helpful, however genetic conformation is always necessary.

EEG abnormalities preceding the epilepsy onset in tuberous sclerosis complex patients - a prospective study of 5 patients.

Tuberous sclerosis complex (TSC) is a multisystem, autosomal dominant disorder characterized by multiple hamartomas development. Epilepsy is the most common symptom appearing in 80-90% of the patients mainly in the first year of life. A prompt and early seizure control is crucial and can prevent development of an epileptic encephalopathy and secondary mental retardation. Therefore the very early identification of seizures seems to be of a great importance. We present the cases of 5 patients diagnosed with TSC prenatally or perinatally and regularly monitored (at 4-6 weeks intervals) with EEG before the epilepsy onset. The patients' age at baseline varied from 9 days to 9 weeks. In all of the patients epileptiform discharges preceded the epilepsy onset. The time interval between abnormality detection on EEG and the epilepsy onset varied from 1 to 8 days. The patient's age at the epilepsy onset ranged from the 17th day to the 5th month of life. In one patient the EEG was abnormal from the beginning and in this patient the epileptic seizures started from the neonatal period. In the rest of the patients (4/5) the EEG remained normal throughout the first months of life. In all of the children epilepsy started with focal motor seizures. Our study is the first prospective one showing the results of the EEG monitoring in TSC patients and the natural evolution of the EEG patterns in patients with the seizures types other than infantile spasms.

Detection of cytomegalovirus in infant cerebrospinal fluid by conventional PCR, nested PCR and PCR-Digene.

The possibility of amplification of human cytomegalovirus (HCMV) DNA in cerebrospinal fluid (CSF) for the diagnosis of HCMV central nervous system (CNS) infection in infants was studied. Single-step PCR, nested PCR and PCR-Digene were used to assay CSF specimens from 37 patients. Criteria for patient inclusion in the study were: 1. clinical manifestations suggesting CMV neuroinfection such as seizures, hypertonia, hypotonia, intracranial calcification, microcephaly, chorioretinitis; 2. any of the following symptoms: anaemia, hepetomegaly, prolonged cholestatic jaundice, or hepatitis, splenomegaly, thrombocytopenia, intrauterine hypotrophy; 3. serologic presentation, and/or positive results for CMV infection obtained by single-step PCR and PCR-Digene in urine and/or blood. PCR-Digene results were positive in 6 CSF samples. Four CSF samples were positive by nested PCR and 1 CSF sample by single step PCR. We found that the double PCR was about ten or more times more sensitive than single PCR and the PCR-Digene was only three times more sensitive than nested-PCR. The results were correlated with serology. Thirty-three out of 37 examined patients were seropositive (ELISA IgG); ELISA IgM gave positive results in 9 patients. In control studies, cells infected with other members of the herpes virus family were negative with these methods, which suggest that amplification combined with primers from the IE and the L-region of CMV is specific. In conclusion, nested-PCR seems to be the best method for early diagnosis of CMV infection in CSF due to an absence of false positive results and its high specificity and sensitivity.

Risk factors for cerebral palsy in very low-birthweight infants in the 1980s and 1990s.

One-hundred twenty-nine very low-birthweight infants were treated in Newborn and Infant Care Department of Children's Memorial Health Institute between 1985 and 1994; 89 were taken to prospective neurodevelopmental care. The newborns were divided into two groups. Group I had 38 preterm infants born from 1985 to 1989 and followed up at 7 to 11 years of age. Group II had 51 very low-birthweight infants treated from 1990 to 1994 and followed up at 2 to 5 years of age. Complicated, multiple pregnancy, normal delivery, and extremely low birthweight were significantly more frequent in group II. Very low-birthweight infants were frequently born by cesarean section in severe asphyxia. Only four (7.8%) newborns received surfactant therapy. From 1990 to 1994, respiratory distress syndrome III and IV, and a longer respiratotherapy period were significantly more frequent. From 1985 to 1994, the frequency of sepsis, periventricular leukomalacia, and normal ultrasonography was constant. Intraventricular hemorrhage I, II, and IV were frequently present in the 1990s, and intraventricular hemorrhage III was frequent in the 1980s. Cerebral palsy was diagnosed in 11 (28.9%) children in group I and 18 (35.2%) in group II (not statistically different). Multiple and complicated pregnancy, cesarean section, severe asphyxia, and respiratory distress syndrome did not increase the risk of cerebral palsy in very low-birthweight infants. Periventricular leukomalacia has a more predictive value for cerebral palsy in these infants than did intraventricular hemorrhage.

[Estimate of clinical dynamic in periventricular leukomalacia]. / Ocena dynamiki objawów klinicznych w przypadkach okolokomorowej leukomalacji.

Clinical observations of 68 preterm and term newborns with ultrasonographically diagnosed PVL treated in the Infant Department of the Child Health Center in Warsaw from January 1985 to December 1990 are presented. The most frequent clinical sign in newborns was hypotonia of the lower extremities. Tremors were significantly more frequent in preterms. During the infant period, more clinical signs occurred in connection with cerebral atrophy (ventriculomegaly and subdural space enlargement). Observations were carried from the neonatal period to the age of 6 years. Development of 42 (61.8%) children was normal. In 26 (38.2%) infants from 6 to 12 months old, cerebral palsy (most frequently diplegia) was diagnosed. No significant differences in the frequency of cerebral palsy between terms and preterms were found. Epilepsy and minimal brain dysfunctions were also present.

[Diagnosis of Edwards syndrome in newborns]. / Diagnostyka zespolu Edwardsa u noworodków--obserwacje wlasne.

Congenital malformations most useful for the diagnosis of trisomy 18 in the first days of life were defined based on observations of newborns with Edwards syndrome treated at the Child Health Center in 1992-1994. Intrauterine growth retardation, facial skeleton dysmorphy, congenital heart malformation, mainly VSD, extremity malformations, especially of the palms and feet found in the newborn suggest a diagnosis of Edwards syndrome. The need to differentially diagnose trisomy 18 with autosomal recessive syndrome TAR, Roberts and Smith-Lemli-Opitz is stressed.