A new microduplication syndrome encompassing the region of the Miller-Dieker (17p13 deletion) syndrome.

BACKGROUND: The use of array comparative genome hybridisation (CGH) analyses for investigation of children with mental retardation has led to the identification of a growing number of new microdeletion and microduplication syndromes, some of which have become clinically well characterised and some that await further delineation. This report describes three children with de novo 17p13.1 duplications encompassing the PAFAH1B1 gene, who had similar phenotypic features, including mild to moderate developmental delay, hypotonia and facial dysmorphism, and compares them to the few previously reported cases with this duplication. METHODS: Multiplex ligation-dependent probe amplification (MLPA) or array-CGH was used to diagnose three developmentally delayed children with duplications of 17p13. The duplications were characterised further using Agilent array technology, revealing duplication sizes from 1.8 to 4.0 Mb, with a region of overlap corresponding to 1.8 Mb. Detailed clinical information was obtained from patient files and personal examinations. RESULTS: The developmental delay and similar clinical features in the three patients were most likely due to a common microduplication of 17p13. CONCLUSIONS: In contrast to patients with deletion of the region (Miller-Dieker syndrome) the patients reported here had mild to moderate retardation and displayed no lissencephaly or gross brain malformations. Further cases with similar duplications are expected to be diagnosed, and will contribute to the delineation of a potential new microduplication syndrome of 17p13.

Gait disturbance interpreted as cerebellar ataxia after MMR vaccination at 15 months of age: a follow-up study.

Measles, mumps and rubella (MMR) vaccination was included in the Danish childhood vaccination programme in 1987. During the following 10-y period, 550 notification records of adverse events after MMR vaccination at 15 mo of age have been registered, and a total of 41 notifications have included "gait disturbance". This corresponds to a frequency of 8 per 100,000 doses of MMR vaccine used for 15-mo-old children. The symptoms and signs are characteristic of cerebellar ataxia. In 28 notifications, the descriptions by the doctors included only "gait disturbance", while in 13 an additional interpretation was included. Thirty-two parents (78%) filled in a questionnaire and 26 (63%) agreed to participate in a clinical follow-up study. The gait disturbance symptoms mainly occurred 7-14 d after the vaccination, and the duration was median 1-2 wk (range 1 d to more than 4 mo). One-third of the children had symptoms lasting more than 2 wk. Significantly more children with long duration of symptoms had some kind of complaint or clinical signs at the follow-up in 1997. Gait disturbance registered after MMR vaccination seems to be more frequent than hitherto reported. Most cases are mild and short-lasting and a longer duration of symptoms seems to be predictive of late sequelae. A clinical diagnosis of cerebellar ataxia after MMR and the exact frequency of this adverse event remains to be tested in prospective studies.

[Molybdenum cofactor deficiency. Clinical symptoms and diagnostic strategy]. / Molybdaen-kofaktormangel. Kliniske symptomer og diagnostisk strategi.

The clinical, neuroradiological and biochemical findings in two siblings with molybdenum cofactor deficiency are presented. A search for this deficiency is advocated in each case of unexplained refractory neonatal convulsions. Early diagnosis is prompted by the often rapid fatal outcome and the availability of methods for prenatal diagnosis. Diagnosis may be missed or delayed on standard metabolic screening for several reasons discussed. Magnetic resonance imaging in this condition seems to be rather characteristic.

Bowel and bladder control of children with myelomeningocele: a Nordic study.

The urinary and bowel control was studied of 527 children with myelomeningocele aged between four and 18 years. Information was obtained from medical records and by parent questionnaire. 44 had normal urinary control, 50 had a urinary diversion and the remaining 433 had neuropathic bladder without urinary diversion, of whom 31 per cent expressed their bladder manually and 40 per cent used clean intermittent catheterisation (CIC). 60 per cent needed assistance emptying their bladder. Children using CIC were more continent and needed less help, but were more often treated with antibiotics. Of the 527 children, 412 had disturbed bowel control. 212 evacuated their bowels manually, of whom 90 per cent needed assistance. Parents judged urinary incontinence to be very stressful for 37 per cent of the children and faecal incontinence for 33 per cent. The authors conclude that social urinary continence should be defined as the ability to keep dry for three hours or more.

Upper extremity function in spina bifida.

Poor upper extremity function is often recorded in meningomyelocele patients. Only 2 of the 25 patients we assessed, 5 to 19 years old, showed normal upper extremity function in the clinical neurological examination and a timed hand function test simulating daily activities. Slow performance with unsystematic variability was typical. Poor hand function correlated strongly with hydrocephalus. A trend towards better performance with increasing age may indicate that the difficulties are overcome in some patients. While patients without hydrocephalus showed a near-normal distribution in the seven subtests, patients with hydrocephalus needed more time than normal children. Patients with shunt-treated hydrocephalus did not cope as well as patients without a shunt. Mean age in the three groups differed and may partly explain the differences.

Intravenous immunoglobulin: a single-blind trial in children with Lennox-Gastaut syndrome.

The antiepileptic effect of intravenous immunoglobulin (Sandoglobulin, Sandoz) was investigated in Lennox-Gastaut syndrome by an add-on, placebo-controlled, single-blind trial. Ten patients, aged 4-14 years, with insufficient response to conventional anticonvulsive therapy received placebo and Sandoglobulin 400 mg/kg two times each with an interval of two weeks. The washout period was four weeks and the total observation period 14 weeks, during which parents daily registered number and type of seizures. EEG, in vitro lymphocyte transformation tests and concentrations of immunoglobulins including IgG subclasses were evaluated before and after active treatment. Two children showed an immediate reduction in their high-frequency and invariable seizure activity from 42% to 100% and a less abnormal EEG. In addition, general well-being and intellectual performance was improved. The strongest response was observed in one child with a concomitant finding of a low level of IgG2, the only abnormal immunologic test in this study. The remaining 8 children, who had either a high or a low but variable seizure frequency showed no immediate change as EEG and their general condition was unaffected. We conclude that intravenous immunoglobulin had an immediate and pronounced effect on break-through seizure activity and a simultaneous neurophysiologic effect in 20% of our patients with Lennox-Gastaut syndrome. The effect was not confined to patients with immunologic abnormalities.

Disability in children with myelomeningocele. A Nordic study.

This study was carried out to evaluate the medical impairments and disability among 527 children with myelomeningocele living in four Nordic countries. The information was extracted form questionnaires and data based on case records. The level of intellectual functioning was fairly high with 76% within normal range (IQ greater than 90). Shunt operations were performed in 68% of the children and 1/3 had had four or more shunt revisions. Twenty-three per cent walked without support. Bladder incontinence was found in 60% of the children whereas 4% were entirely continent. Intermittent catheterisation was used in 36% with higher frequency among girls (48%) than boys (24%). We found a higher incidence of bacteriuria among those who used catheterisation than among those who used manual compression. Bowel control was experienced by 112 (21%) of the children. The overall disability is classified according to Lorbber's 5-graded handicap scale and Lagergren's 3-graded scale. According to Lagergren's scale, 70% suffered form severe overall disability.

Cerebral blood flow abnormalities in cerebral palsied children with a normal CT scan.

Cerebral palsy (CP) is often a consequence of a hypoxic-ischemic encephalopathy and/or intracerebral hemorrhage secondary to pre- and peri-natal asphyxia. Hypodense lesions on the CT-scan are found in about 70 to 80% of CP-patients. In the present study, regional cerebral blood flow (CBF) was measured in CP-patients having a normal CT-scan. The aim was to correlate the CBF changes with the clinical and the etiologic findings. CBF was measured by xenon-133 inhalation and single photon emission computer tomography. The mean CBF value in 20 CP-patients, age 6-19 years, was 67 +/- 11 (1 SD) ml/100g/min, the same value as found in the 9 normal children. However, 16 of the 20 CP-patients had focal hypoperfused areas on the tomographic flow map. In the preterm infants (n = 7) the hypoperfused areas were mainly located in the posterior watershed areas, often in one hemisphere only. In the term infants (n = 13) both asymmetrical and symmetrical hypoperfused areas were observed in the anterior and posterior watershed areas. In addition, several children had larger low flow areas in the frontal and fronto-parietal lobes. In both groups, a relatively poor concordance was observed between the clinical findings and the expected location of the low flow area.

Prophylactic treatment with valproic acid or diazepam in children with febrile convulsions.

The purpose of this study was to limit prophylactic treatment of children with febrile convulsions to patients who have the highest risk of recurrence. Two hundred and thirty-one children with a first febrile seizure were divided into high- and low-risk groups according to estimated risk of recurrence. All high-risk children were offered treatment with valproic acid. If this was declined they were offered treatment with diazepam instead. Low-risk children were untreated. Valproic acid and diazepam were found to be equally effective in reducing the risk of recurrence of febrile convulsions. By selecting for prophylactic treatment according to estimated risk of recurrence it is possible to reduce the rate of recurrence of febrile seizures in children at high-risk (60%) to the same level as that of untreated low-risk children (23%). Only about half of all children with febrile convulsions need treatment and follow-up according to these criteria.

Spontaneous remission of cerebral palsy.

Among 2100 children with a diagnosis of cerebral palsy (CP) twenty carried the diagnosis: Previous CP, now normalized. Seventeen patients could be traced and were reevaluated. Cerebral palsy was diagnosed in these seventeen children (ten boys, seven girls) between the ages of three months and three years (average eleven months). They were found to be normal when reexamined between the ages of one year and five years (average two years two months). Two patients had tetraplegia, three diplegia, nine paraplegia ("paraplegia" were cases of diplegia with minimal affection of the upper limbs - now called "diplegia type I"), and one hemiplegia. One patient had atactic diplegia, and one was athetotic. The records of these seventeen patients were evaluated with respect to aetiology and symptomatology. Upon reexamination seven patients were found to be completely normal. Five patients had no motor symptoms but showed signs of specific neuropsychological difficulties. Two patients were intellectually retarded without motor symptoms. One showed signs of neuropathy, and one had fetal alcohol syndrome. Signs consistent with CP could be demonstrated in one patient only. This study shows that signs of CP may in rare cases disappear altogether.

Alloimmune neonatal thrombocytopenia and hydrocephalus. Platelet antigen Zwa, ABO-antigens and HLA-antigens in mothers to infants with hydrocephalus.

In 27 mothers to infants with hydrocephalus determinations of platelet antigen Zwa, HLA-typing and ABO-typing were performed in order to evaluate whether undiagnosed alloimmune neonatal thrombocytopenia (AINT) could be an aetiological factor in hydrocephalus. All mothers were Zwa-positive, and the frequency of HLA-antigens and ABO-antigens was as in the normal population. Though sporadic cases of hydrocephalus following AINT are reported, this is not a common cause of intracranial haemorrhage and hydrocephalus.

CT findings in spastic cerebral palsy. Clinical, aetiological and prognostic aspects.

After the introduction of cranial computed tomography (CT) it is now possible by an atraumatic procedure to evaluate the pathophysiological findings in children suffering from cerebral palsy (CP). The aim of this study is to describe the cranial CT findings in children with CP and relate these to CP-type, grade of handicap, aetiology, and presence of other functional cerebral defects. The CT-examination was performed in 83 children with spastic CP (44 boys and 39 girls). Fifty-seven children (67%) had pathological CT. There was no statistically significant difference between the frequencies of pathological CT findings in the groups with tetraplegia, diplegia, and paraplegia. The frequency of pathological CT findings was increasing with increasing severity of the motor handicap (p less than 0.05). There were significantly more children with pathological CT findings among CP children suffering from epilepsy, than among CP children without epilepsy (p less than 0.05). The CP children with the lowest IQ, had numerical more pathological CT findings but there was no significant difference among pathological CT findings in CP children with oligophrenia compared to the rest of the group. Infarction, its sequelae and hemiatrophy were much more frequent in patients with hemiplegia (p less than 0.001) compared to the other CP-types. The most frequent pathological CT finding was atrophy (44 cases among 56 pathological CT). Central atrophy with enlargement of the ventricular system or parts of this was found in 39 children.(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomography in spastic cerebral palsy.

Eighty-three children with spastic cerebral palsy (CP) were examined with cranial CT. In 56 cases the CT findings were abnormal. The most frequent abnormality was atrophy, present in 44 patients. The frequency of pathologic CT increased with severity of the CP. Patients with CP of postnatal aetiology more often had abnormal CT than patients with other known causes. Pathologic CT findings were seen more often in patients with seizures than in patients without. Infarctions and hemiatrophy were much more frequent in patients with hemiplegia than in patients with other types of spastic CP. A special kind of central atrophy, called isolated atrophy around in the cella media, is described. This condition was seen in 20% of cases, most often in hemi- and paraplegic patients. Early infarctions in the border areas between the vascular territories of the internal carotid and the posterior cerebral artery may be the reason for this kind of atrophy.