Stress in Parents of Children With Genetically Determined Leukoencephalopathies: A Pilot Study.

Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index-4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index-4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.

Neurofibromatosis type 1 in a pediatric population: Ste-Justine's experience.

BACKGROUND: To date, few pediatric series of neurofibromatosis type 1 (NF-1) have been described in the literature even though it is the most frequently encountered phakomatosis. METHODS: We reviewed 987 charts of pediatric patients with a presumptive diagnosis of NF-1 who were evaluated at Ste-Justine hospital from January 1, 1991 to July 31, 2002. Patients who presented with two or more cardinal criteria were diagnosed with NF-1. Clinical and laboratory data were retrospectively collected, including: demographics, neuroimaging and presence or absence of associated symptoms or signs of NF-1. RESULTS: A total of 279 patients were diagnosed with NF-1. The mean age at diagnosis was 3.4 years. Ninety-nine percent of the patients had café au lait spots and 47% had a first degree relative with NF-1. Almost 60 percent (59.6%) of those seen by an ophthalmologist had Lisch nodules. Optic glioma was found in in 14.7%, cutaneous neurofibromas in 38.4%, plexiform neurofibromas in 24.7%, neurofibrosarcoma in 1.8%, learning disabilities in 39%, attention deficit disorder in 40.5%, osseous dysplasias in 7.2%, pseudoarthrosis in 3.6%, precocious puberty in 3.2% and short stature in 17.9%. Magnetic resonance, when performed, showed hyperintense T2 lesions in 87.1% of cases. The mean period of follow-up was 7.4 years. CONCLUSION: Neurofibromatosis type 1 is a multisystemic disorder associated with increased risk of malignancy. It can be diagnosed at a very young age and clinical follow-up is advised. To our knowledge, this is the largest single center study of NF-1 in a pediatric population.

Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in French Canadians.

BACKGROUND: Hereditary sensory and autonomic neuropathy type 2 (HSAN2; MIM 201300) is a rare recessive neuropathy typically diagnosed in the first decade. The 1973 study of a French Canadian family led to the definition of HSAN2. OBJECTIVES: To demonstrate that the apparent higher prevalence of HSAN2 in Quebec is due to the presence of two HSN2 mutations and that carriers of different mutations appear to have a similar phenotype. METHODS: Through attending physicians, the authors recruited French Canadian patients with HSAN2. Exclusion of linkage to the known HSAN loci and linkage to the HSAN2 was performed using standard methods. Sequencing of the HSN2 gene was used to uncover the causal mutations. RESULTS: A large cluster of HSAN2 patients comprising 16 affected individuals belonging to 13 families was identified. The mode of inheritance is clearly autosomal recessive. All patients originated from southern Quebec, and 75% are from the Lanaudière region. Whereas linkage to the HSAN1, 3, and 4 loci was excluded, linkage to the 12p13.33 HSAN2 locus was confirmed. Sequencing of the HSN2 gene uncovered two French Canadian mutations and a novel nonsense mutation in a patient of Lebanese origin, all predicted to lead to truncations of the HSN2 protein. The comparison of clinical variables between patients with different genotypes does not suggest any difference in phenotype. CONCLUSIONS: Two founder mutations are responsible for the apparently higher prevalence of HSAN2 in French Canadians. Genotype-phenotype correlation does not suggest any significant clinical variability.

Stroke in children: the coexistence of multiple risk factors predicts poor outcome.

OBJECTIVE: To characterize the risk factors for stroke in children and their relationship to outcomes. METHODS: We reviewed charts of children with ischemic and hemorrhagic stroke seen at Hopital Sainte-Justine, Montreal between 1991 and 1997. RESULTS: We found 51 ischemic strokes: 46 arterial and 5 sinovenous thromboses. Risk factors were variable and multiple in 12 (24%) of the 51 ischemic strokes. Ischemic stroke recurred in 3 (8%) patients with a single or no identified risk factor and in 5 (42%) of 12 patients with multiple risk factors (p = 0.01). We also found 21 hemorrhagic strokes, 14 (67%) of which were caused by vascular abnormalities. No patient with hemorrhagic stroke had multiple risk factors. Hemorrhagic stroke recurred in two patients (10%). Outcome in all 72 stroke patients was as follows: asymptomatic, 36%; symptomatic epilepsy or persistent neurologic deficit, 45%; and death, 20%. Death occurred more frequently in patients with recurrent stroke (40%) than in those with nonrecurrent stroke (16%). CONCLUSIONS: Multiple risk factors are found in many ischemic strokes and may predict stroke recurrence. Recurrent stroke tends to increase rate of mortality. Because of the high prevalence and importance of multiple risk factors, a complete investigation, including hematologic and metabolic studies and angiography, should be considered in every child with ischemic stroke, even when a cause is known.

Hypothalamic dysfunction in a child: a distinct syndrome? Report of a case and review of the literature.

We report the case of a 9-year-old girl with multiple problems due to hypothalamic dysfunction of obscure origin: apnoeic spells, behavioural problems, developmental delay, hypodipsia with bouts of hypernatraemia, episodes of spontaneous hypothermia, obesity, petit-mal seizures, non-progressive precocious puberty, absence of respiratory response to CO2 and probably insensitivity of hyposensitivity to pain. She also had hyperprolactinaemia and decreased human growth hormone secretion. Hypothyroidism of central origin and hyposecretion of cortisol were also present. Multiple brain CT-scans failed to reveal any tumour or other anatomical abnormality. Her clinical course was improved initially by treatment with clomipramine, but she died suddenly, and the autopsy failed to disclose any anatomical lesion. We compare this case with three similar previously reported cases.

Intramedullary epidermoid cysts of the spinal cord. Case report.

Epidermoid cysts are tumors familiar to neurosurgeons, but intramedullary epidermoid cysts are rare. The authors report the case of a 6-year-old girl presenting with progressive paraparesis. A midthoracic intramedullary mass was revealed on myelography and magnetic resonance (MR) imaging and confirmed as an intramedullary epidermoid cyst at surgery, at which time the cyst was removed. This is the fourth report documenting a purely intramedullary epidermoid cyst occurring in a child. The pathology and etiology, epidemiology, clinical features, radiology (including MR image characteristics), and surgical treatment of such rare intramedullary benign tumors are discussed. Magnetic resonance imaging reduces the delay in diagnosis of spinal cord tumors but should be guided by clinical judgment.

Neurologic crises in hereditary tyrosinemia.

Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi's syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.

Congenital malformations associated with maternal use of valproic acid.

Two children born with birth defects after intrauterine exposure to valproic acid are reported. The mothers took the drug throughout pregnancy as sole treatment for primary generalized epilepsy. The first baby showed facial dysmorphism, arachnodactyly and triphalangeal thumbs. The second had facial dysmorphism, severe laryngeal hypoplasia, tracheomalacia and an aberrant innominate artery that caused tracheal compression. A left superior vena cava, abnormal pulmonary lobulation, and unilateral hydronephrosis were also found at autopsy. Valproic acid has probable teratogenic potential in humans but the number of reported cases is few and the spectrum of anomalies is broad so it is not possible to delineate a definite fetal valproate syndrome.

Femoral neuropathy after renal transplantation.

We report 2 cases of cadaveric renal transplantation in which the grafts were placed in the right iliac fossa. Postoperatively, both patients complained of ipsilateral thigh weakness. Electromyography and nerve conduction studies indicated femoral nerve neuropathy. Muscle weakness gradually resolved. Difficulty was encountered in placing both grafts, and each kidney and limb were subjected to prolonged ischemia. We suggest that the femoral neuropathy was ischemic in origin.

Intermittent treatment of febrile convulsions with nitrazepam.

Intermittent oral or rectal administration of diazepam for the prophylactic treatment of febrile convulsions has given results comparable to the continuous use of phenobarbital while limiting side effects and risks of toxicity. Since we believe that nitrazepam is a better anticonvulsant than diazepam, we performed a study to evaluate the effectiveness of this medication in the prophylactic treatment of febrile convulsions. Nitrazepam was given only when the children had fever and almost exclusively in children with a high risk of recurrence (less than 12 months of age at first convulsion; atypical convulsion; one or several previous convulsions). Thirty one children with a high risk of recurrence received nitrazepam. The rate of recurrence in this group was 19.3% after a follow-up of 16 months, compared to 45.8% in 24 children who also had a high risk of recurrence but in whom the parents refused the medication or gave it inadequately (p less than 0.05). Fifty one children with a low risk of recurrence also were evaluated and followed for at least 12 months (mean 15.4 months). Six were treated with nitrazepam, mostly because of parental anxiety, and none had a recurrence; of the 45 untreated children in this group, 6 (13.6%) had another convulsion. These results show the efficiency of nitrazepam in the prophylactic treatment of febrile convulsions.

The Andermann syndrome: agenesis of the corpus callosum associated with mental retardation and progressive sensorimotor neuronopathy.

Andermann et al. described in 1972 an autosomal recessive inherited syndrome which associates agenesis of the corpus callosum, mental deficiency, and a peripheral motor deficit. We had the opportunity to study in detail 15 patients affected by this syndrome. As in the cases previously reported, the families of these children all originated from Charlevoix County and the Saguenay-Lac St-Jean area in the Province of Quebec. Clinically, these patients have a characteristic facies and moderate mental retardation associated with a progressive motor neuropathy leading to loss of ambulation by adolescence and progressive scoliosis. In 13 of these 15 patients, neuroradiological investigation has shown either total or partial agenesis of the corpus callosum. In every patient in whom these tests were done, sensory nerve action potentials were absent and motor nerve conduction velocities reduced. We also found neurogenic abnormalities both on EMG and neuromuscular biopsies. These abnormalities are similar to those described in Friedreich's ataxia and in hereditary motor and sensory neuropathy type II, although in our patients the motor deficit is much more severe than in these diseases. The pathogenesis of the peripheral nervous system involvement is still unknown since there have so far been no autopsy studies of this syndrome.

Benign familial neonatal convulsions.

Benign familial neonatal convulsions are a rare genetic seizure disorder inherited as an autosomal dominant trait. They consist of brief episodes of seizures, recurring during the first few days or weeks of life in otherwise normal babies; their prognosis is good. We report a family in which at least 12 members in three generations presented with this condition; they all had an excellent outcome.

Fragile X chromosome and X-linked mental retardation.

A family is described in which three normal females transmitted to seven males X-linked mental retardation associated with macro-orchidism and a fragile site on the long arm of the X chromosome -- fra(X)(q27). The affected males also had minor clinical features in common: a large forehead, long face, large ears, a long upper lip and large extremities.

Rud syndrome: congenital ichthyosis, hypogonadism, mental retardation, retinitis pigmentosa and hypertrophic polyneuropathy.

Rud syndrome consists in the association of oligophrenia and hypogonadism with congenital ichthyosis; in the majority of cases, epilepsy, short stature or delayed in growth are also found. We described a child with such a syndrome. In addition to the classical findings, the patient had retinitis pigmentosa and hypertrophic polyneuropathy. Histological studies, including ultrastructural findings of a sural nerve biopsy, showed signs of a chronic demyelinative neuropathy with onion bulb formation. The world literature was reviewed and only nine other cases fulfilled our criteria for inclusion in Rud syndrome. This case represents the one with the most extensive neurological involvement ever reported.

[Trichopoliodystrophy or Menkes disease]. / Trichopoliodystrophie, ou la maladie de Menkes.

Trichopoliodystrophy (also known as Menkes' kinky or steely hair disease), a recessive sex-linked syndrome, is characterized by severely retarded mental and physical development, convulsions, a particular phenotype and abnormalities of the hair, bones and arteries. Very low levels of copper and ceruloplasmin in the serum confirm the diagnosis. This rare disorder is caused by an inborn error of copper metabolism whose nature is not yet clear. Recent hypotheses favour either an abnormality in the transport of copper across the cell membrane or increased affinity for copper of the intracellular binding protein. Because the metabolic abnormality is expressed autonomously and irregularly in various tissues, the distribution of copper within the body is disordered. Up to now none of the many forms of copper therapy has succeeded in modifying the fatal course of the disease in humans. This article presents a new case, the first in Canada, and a review of the other 69 cases described in the literature. The new case illustrates, in addition to the classic picture, less well known features, such as diverticula of the bladder mucosa and serosa, as well as cortical atrophy and malformed cerebral vessels demonstrated by computer-assisted tomography.

[Type 1 fucosidosis. Anatomical study]. / Fucosidose de type 1. Etude anatomique.

The first Canadian child with complete absence of alpha L-fucosidase is described. The neurological course was characterised by rapid deterioration and he died at the earliest age recorded so far. There are only two published reports of autopsies in this condition to which we add another, together with the ultrastructural findings of a liver biopsy.

[Neuronal ceroid-lipofuscinosis. Diagnosis by skin biopsy. Physiopathology (author's transl)]. / Ceroidolipofuscinosis neuronal. Diagnóstico por biopsia cutánea. Fisiopatología.

Authors report a case of Batten's disease (neuronal ceroid-lipofuscinosis), in its late infantile form (Jansky-Bielschowsky), so as the ability to identify the process by ultrastructural study of the skin.