Cognitive and behavioral functioning in two neurogenetic disorders; how different are these aspects in Duchenne muscular dystrophy and Neurofibromatosis type 1?

The presence of neurocognitive and behavioral problems are common features in various neurogenetic disorders. In Duchenne muscular dystrophy (DMD), these problems have been linked to mutations along the dystrophin gene affecting different brain dystrophin isoforms. However, comparable cognitive and behavioral problems have been found in Neurofibromatosis type 1 (NF1). This study aims to assess disorder specific differences in cognition and behavior between DMD and NF1. Retrospective data of 38 male patients with DMD were aged-matched with data of 38 male patients with NF1. Patients of both groups underwent neurocognitive assessment for regular clinical care. Intellectual abilities, sequential and simultaneous processing, verbal memory and sustained attention were evaluated. In addition, parents and teachers completed behavioral questionnaires. Males with DMD exhibited low intellectual abilities and sequential processing problems, but these outcomes not significantly differed from males with NF1. Simultaneous processing, verbal memory and sustained attention outcomes were equal for both groups. Outcomes of questionnaires displayed higher rates of aggressive behavior (13.2%) in DMD, whereas in NF1 higher rates of problems with thinking (15.8%), withdrawn (10.5%) and social behavior (10.5%) were noticed. In the neurogenetic disorders DMD and NF1, on average overlapping cognitive and behavioral problems are noticed, suggesting that these are not only caused by gene mutations resulting in a lack of one specific protein.

Microduplication 22q11.2: a benign polymorphism or a syndrome with a very large clinical variability and reduced penetrance?--Report of two families.

We report on two unrelated families where the probands presented with learning difficulties and a microduplication 22q11.2. In the first family the proband was a 7-year-old boy who was referred because of psychomotor retardation, behavioral problems, large weight and height, and mild dysmorphism. His father and one brother also had mental retardation and behavioral anomalies, and presented the same microduplication. In the second family only the proband had mild learning difficulties, but the same microduplication 22q11.2 was discovered in her sister, her asymptomatic mother and grandfather. No distinctly recognizable phenotype has been observed in the individuals from our two families diagnosed with microduplication 22q11.2. The marked clinical variability both inter- and intrafamilial, including the presence of a complete normal phenotype and the presence of high intellectual possibilities in two individuals with this microduplication 22q11.2 is remarkable. So far, 63 patients, corresponding to 35 families, with microduplication 22q11.2 have been described. The fact that microduplication 22q11.2 can be seen in individuals with a normal/near normal phenotype has been previously reported as well. We postulate that the clinical findings described so far could be due to ascertainment bias, since the most common reason for performing FISH 22 analyses is to exclude microdeletion. Future reports are needed to answer the question whether microduplication could be a non-pathogenic polymorphism or whether it is a real syndrome with a very large clinical variability and reduced penetrance.

Streptococcus pneumoniae meningoencephalitis with unusual and widespread white matter lesions.

Streptococcus pneumoniae is a common cause of bacterial meningitis, frequently leading to death or severe neurological impairment. We report an exceptional case of a 7-month-old child with meningoencephalitis caused by S. pneumoniae. Peculiar, widespread and unique signal abnormalities were found on magnetic resonance imaging (MRI) with extensive central nervous white matter injury as well as evidence of thrombosis of the lateral transverse sinus. These changes were observed very early in the course of the illness, presumably reflecting widespread cytotoxic edema, vasculitis and acute demyelination. These lesions occurred despite appropriate antibiotic and anti-inflammatory (glucocorticoid) therapy started very early in the course of the disease. Such diffuse white matter lesions in the early course of (pediatric) cases of S. pneumoniae meningoencephalitis have not been reported previously.

Can IQ predict parent-reported behavioral and emotional problems in children with neurological deficiencies?

OBJECTIVE: The aim of the current study was to investigate whether total intelligence scores (FSIQ) and/or a discrepancy in intelligence can predict behavioral or emotional problems in children with neurological deficiencies. METHOD: The population consists of children with neurological deficiencies (N = 610, ranging from 6 to 17 years), referred due to concerns on the (educational) development of the child to a tertiary outpatient clinic. All children were tested with the Dutch Wechsler Intelligence Scale for Children - third edition (WISC-III-NL). A VIQ-PIQ discrepancy score was calculated by subtracting the performance capacities of the verbal capacities. The effects of demographic variables, FSIQ, and the VIQ-PIQ discrepancy on two parent-rated questionnaires measuring behavior and emotions in children were analyzed with linear and logistic regression models. RESULTS AND CONCLUSION: The VIQ-PIQ discrepancy was not predictive of behavioral or emotional problems recorded on the above-mentioned parent-rated questionnaires. The FSIQ score, age, and sex were predictive to some extent: increases in age and FSIQ led to a decrease of reported problems, and boys showed more problems than girls. Children with neurological deficiencies had on average significantly higher verbal capacities than performance capacities, in line with the neuropsychological principle that language survives brain damage whereas performance capacities are more affected.

Opisthotonus and intrathecal treatment with baclofen (ITB) in children.

Opisthotonus is a relatively rare, but challenging neurological symptom of spasticity or dystonia that most often results from a dramatic event such as near-drowning. The classic treatment option for opisthotonus is the oral administration of medication such as benzodiazepines and baclofen. However, results with these medications are usually not very beneficial. Numerous studies however have shown that intrathecal treatment with baclofen (ITB) is an efficient and safe treatment for generalized therapy-resistant spasticity, even in children. In this retrospective study, we describe 11 children (mean age 9 years) with pronounced opisthotonus and quadriplegia caused by different types of acquired lesions who were treated with intrathecal baclofen. Results show that in addition to an expected decrease in muscle tonus, there was also a clear improvement in patient comfort and nursing. A remarkable weight gain was observed in most patients, even when calorie intake did not change. This increase in weight might be due to a reduction in energy expenditure as a result of the decrease in spasticity. Intrathecal treatment with baclofen should be considered in every child with opisthotonus.

Clinical report of a pure subtelomeric 1qter deletion in a boy with mental retardation and multiple anomalies adds further evidence for a specific phenotype.

Deletions of the 1q telomere have been reported in several studies screening for subtelomeric rearrangements. However, an adequate clinical description is available from only a few patients. We provide a clinical description of a patient with a subtelomeric deletion of chromosome 1q, previously detected by us in a screening study. Comparison of the clinical presentation of our patient with rare cases reported previously provides further evidence for a specific phenotype of 1q patients, including mental retardation, growth retardation, sometimes with prenatal onset, progressive microcephaly, seizures, hand and foot abnormalities and a variety of midline defects, including corpus callosum, cardiac, genital and gastro-esophageal abnormalities. This clinical presentation is reminiscent of that of patients with larger, microscopically visible deletions of chromosome 1q (>3 Mb) characterized by growth and mental retardation, coarse faces with thin upper lip, epilepsy, and variable other anomalies. In addition, the breakpoint region was mapped to a 26 kb region within the RGS7 gene. Among the 17 known genes in the candidate region, are zinc-finger genes. Other members of this gene family have been implicated in different forms of mental retardation.

Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI.

Shaken-baby syndrome (SBS) is a type of child abuse caused by violent shaking of an infant, with or without impact, and characterized by subdural hematomas, retinal hemorrhages, and occult bone fractures. Parenchymal brain lesions in SBS may be missed or underestimated on CT scans, but can be detected at an earlier stage with diffusion-weighted MRI (DW-MRI) as areas of restricted diffusion. We demonstrate the value of DW-MRI in a 2-month-old baby boy with suspected SBS. The pattern of diffusion abnormalities indicates that the neuropathology of parenchymal lesions in SBS is due to hypoxic-ischemic brain injuries, and not to diffuse axonal injury.