Duplication of 15q11.2-q14, including the P gene, in a woman with generalized skin hyperpigmentation.

We describe a woman with 15q11.2-q14 duplication who had clinical manifestations of proximal 15q trisomy and hyperpigmentation. Within this region, the P gene, located at chromosome segment 15q11.2-q12, is associated with oculocutaneous albinism type II (OCA2) and with hypopigmentation in the Prader-Willi and Angelman chromosome 15q deletion syndromes. We therefore hypothesized that in this woman skin hyperpigmentation might result from a duplication of the P gene. We carried out chromosomal and interphase fluorescence in situ hybridization (I-FISH) analyses, and determined that the P gene is duplicated in this woman. Our findings demonstrate that trisomy of the P gene can be associated with skin hyperpigmentation.

Woman with UV hypersensitivity and a de novo unbalanced chromosome translocation.

We report a Japanese woman with de novo 6p monosomy and 10q trisomy [46,XX,der(6)t(6;10)(p25.1;q25.2)] whose clinical manifestations resemble those of xeroderma pigmentosum (XP) and Cockayne syndrome (CS), known as premature aging syndromes. She had a history of easy sunburning and presented a number of freckles and hypopigmented spots on her face as those of XP. Magnetic resonance imaging and computed tomography scanning demonstrated intracranial abnormalities like those seen in CS. DNA repair studies using the patient's fibroblasts demonstrated hypersensitive responses to ultraviolet (UV). XP, CS, and UV-sensitive syndromes with photosensitivity disturbances have been known as DNA repair abnormalities. However, an association of 6p monosomy with these diseases has not been reported so far. Molecular analysis of the patient we described may contribute to the identification of novel DNA-repair-related gene(s) and/or to the senile mechanism.

Complicated hereditary spastic paraplegia with peripheral neuropathy, optic atrophy and mental retardation.

An 8-year old girl with a not previously described type of complicated hereditary spastic paraplegia (HSP) is presented. Spasticity in her lower limbs had already been recognized during infancy and worsened progressively. Severe delay in mental development was observed. Peripheral neuropathy and optic atrophy developed at 5 years of age. On brain magnetic resonance imaging, an abnormally thin corpus callosum was observed. Involvement of the fasciculus gracilis was suggested by somatosensory evoked potentials. To our knowledge, there has been no reported case of complicated HSP with peripheral neuropathy, optic atrophy and mental retardation so far. We postulate that our patient is a sporadic case of not previously described complicated HSP.

Monotherapy for childhood epilepsies with zonisamide.

Zonisamide was tried on 44 children, 18 girls and 26 boys, from 8 months to 15 years of age at the start of the trial. In 6 children the drug has been stopped because of side effects. The drug was introduced at a dose of 2-4 mg/kg/day and increased to 12 mg/kg/day unless a satisfactory response occurred at a lower dose. A 100% control of seizures was achieved in 5 of 5 cases of idiopathic generalized epilepsies, in 7 of 8 cases of symptomatic generalized epilepsies, in one of one case of idiopathic partial epilepsies, and in 17 of 24 cases of symptomatic partial epilepsies. The main side effect was drowsiness, especially during the introduction.

Long-term prognosis of complex partial seizures in childhood.

We studied the long-term prognosis of complex partial seizures in childhood including their electroencephalograms, behavioral problems and adaptation to school or society. In the clinical course, seizures were controlled in 25 cases out of 40 (62.5%). The rate of seizure control was significantly higher in cases with a past history of febrile convulsions, whose onset occurred before 6 years of age and in whom the CT scans were normal. Behavioral, motor and emotional problems included "clumsiness" in 25%, "poor athletes" in 22.5%, "hyperactivity" in 17.5% and "easily enraged" in 12.5% of the cases. The overall cooperation of the surroundings with the patients was thought to be as important a factor as the patients' IQ, motor or emotional problems so that they can get along in school or society.