The Angelman syndrome (AS) is a neurological disorder characterized by severe mental retardation, absent speech, seizures, gait disturbances, and a typical age-dependent facial phenotype. Most cases are due to an interstitial deletion on the maternally inherited chromosome 15, in the critical region q11-q13. Rare cases also result from paternal uniparental disomy of chromosome 15. In a group of 14 patients with sporadic AS diagnosed in Switzerland, we found 2 unrelated females with paternal isodisomy for the entire chromosome 15. Their phenotypes were milder than usually seen in this syndrome: one girl did not show the typical AS facial changes; both patients had late-onset mild seizures; as they grew older, they had largely undisturbed gross motor functions, in particular no severe ataxia. Both girls were born to older fathers (45 and 43 years old, respectively). The apparent association of a relatively milder phenotype in AS with paternal uniparental disomy will have to be confirmed by detailed clinical descriptions of further patients.

The prognostic significance of magnetic resonance imaging (MRI) in the neonatal period was studied prospectively in 43 term infants with perinatal asphyxia. MRI was performed between 1 and 14 days after birth with a high field system (2.35 Tesla). Neurodevelopmental outcome was assessed by a standardized neurological examination and the Griffiths developmental test at a mean age of 18.9 months. The predictive value of the various MRI patterns was as follows: Severe diffuse brain injury (pattern AII+III; n = 7) and lesions of thalamus and basal ganglia (pattern C; n = 5) were strongly associated with poor outcome and greatly reduced head growth. Mild diffuse brain injury (pattern AI; n = 7), parasagittal lesions (B; n = 7), periventricular hyperintensity (D; n = 2), focal brain necrosis and hemorrhage (E; n = 3) and periventricular hypointense stripes (on T2-weighted images; F; n = 3) led in one third of the infants to minor neurological disturbances and mild developmental delay. Infants with normal MRI findings (G; n = 9) developed normally with the exception of one infant who was mildly delayed at 18 months. The results indicate that MRI examination during the first two weeks of life is of prognostic significance in term infants suffering from perinatal asphyxia. Severe hypoxic-ischemic brain lesions were associated highly significantly with poor neuro-developmental outcome, whereas infants with inconspicuous MRI developed normally.

We describe three children born at term investigated for neonatal seizures or transient apnoea. Cranial ultrasound and MRI unexpectedly revealed symmetrical periventricular cysts adjacent to the anterior horns. We found no evidence of prenatal viral infection, intraventricular or subependymal haemorrhage or hypoxic-ischaemic lesions. The lesions were not seen on MRI at 3 months of age, but there was no compensatory dilatation of the anterior horns nor secondary loss of white matter. The appearance and location of these transient cysts were different from those of the cystic changes which typically follow germinal matrix haemorrhage or periventricular leukomalacia. Their pathogenesis and clinical significance remain to be determined.

The effect of radio- and chemotherapy on auxological parameters was investigated in 30 children treated for acute lymphatic leukemia (ALL) or non-Hodgkins lymphoma (NHL). Growth velocity was decreased during the first year of treatment. Catch-up growth was insufficient during the following years. Thus, the whole group experienced a loss of height of 0.49 ± 1.1 SD at 6.8 ± 2.6 years after diagnosis. Height and growth velocity were not different between children who received 18 or 24 Gy cranial irradiation; however, growth velocity was significantly lower in children who were treated for more than 2 years or who had the more intensive chemotherapeutic protocol. Evaluation of the growth hormone (GH) response to pharmacological stimulation revealed reduced GH peaks in 47% of the patients, but there was no correlation of GH peak with growth or treatment parameters. In conclusion, the impairment of growth in children after treatment for ALL or NHL might be related to the intensity and duration of chemotherapy.

Between 1989 and 1993, somatosensory evoked potentials (SEP) were recorded as part of the diagnostic work-up in 282 children with different neurologic disorders. In thirty-one children with N20/P25/N35 amplitudes were enhanced compared to our control group (highest amplitude 14.1 microV). Four children had amplitudes > 40 microV ("giant"), fifteen between 20-39.9 microV ("elevated") and twelve between 14-19.9 microV ("borderline"). Enhanced cortical SEPs were seen in all patients with neuronal ceroid lipofuscinosis (5 late-infantile NCL > 20 microV, 1 juvenile NCL 14.7 microV). In addition, five of six NCL children showed bilaterally prolonged cervico-cortical conduction times, otherwise only seen in a 4-month-old child following hypoxia. "Borderline" and "elevated" SEPs occurred in patients with heterogeneous neurologic disorders. Follow-up recordings showed inconsistent results: seven children had amplitudes > 14 microV in all recordings, six only at the first examination, and six only at follow-up. In six children with hemiparesis enhanced SEPs were recorded over both (n = 2) or only over the unaffected hemisphere (n = 4). Myoclonic seizures were observed only in five children with NCL. Similar to other SEP parameters, enhanced amplitudes are an unspecific indicator of an ongoing neurologic disorder. However, in neuronal ceroid lipofuscinosis, enhanced SEP amplitudes may be a useful diagnostic criterium.