A child with macrocephaly: case report of a patient with megalencephalic leukoencephalopathy with subcortical cysts and a compound heterozygosity for two mutations in the MLC1 gene.

Megalencephaly is as a rule accompanied by macrocephaly, an occipitofrontal circumference (OFC) greater than the 98th percentile. Megalencephaly is divided into an anatomic type (developmental) and a metabolic type. Metabolic megalencephaly refers to various storage and degenerative encephalopathies. The differential diagnosis includes Alexander's disease, Canavan's disease, glutaric aciduria type 1, GM1 and GM2 gangliosidosis, merosin-deficient variant of congenital muscular dystrophy and megalencephalic leukoencephalopathy with subcortical cysts (MLC). The distinctive features of this syndrome are enlarged cranial circumference, present at birth or starting in the first year of life, and magnetic resonance imaging (MRI) evidence of diffuse with matter abnormalities with subcortical cysts in the tips of the temporal lobes and in frontoparietal subcortical areas. Mutations in the MLC1 gene have been found as causative of MLC in 60-70 % of affected subjects, without genotype-phenotype correlation. The child we describe presented with progressive macrocephaly not associated with dysmorphic features and large abdominoscrotal hydrocele. At the age of 8 months, encephalic MRI showed anomalies suggestive for MLC and brainstem auditory evoked potentials (BAEP) documented alterations of signal conduction in right tracts. At the time, clinical neurologic examination was normal. Extensive metabolic assays were within normal range. Sequence analysis for MLC1 gene revealed a compound heterozygosity for two mutations in MLC1 gene, inherited from healthy non consanguineous parents.

Kenny-Caffey syndrome in two sibs born to consanguineous parents: evidence for an autosomal recessive variant.

We report on 2 sibs with manifestations of the Kenny-Caffey syndrome born to normal, consanguineous parents. Clinical manifestations included dwarfism, internal cortical thickening and medullary stenosis of tubular bones, poorly ossified skull bones, and hypocalcemia. The younger of the two died during a tonic convulsion. The older had neonatal hypoparathyroidism and is now a short intelligent, 1-year-old child. This family gives new support to the existence of an autosomal recessive variant of the syndrome.

[Carnitine and Down's syndrome]. / Carnitina e sindrome di Down.

The present study revealed a degree of carnitine deficiency in a large percentage of Down's syndrome children. In fact below average carnitine levels were noted in 39.1% of the cases examined with severe deficiency in 4. On the basis of these data supplementary carnitine is recommended in cases of deficiency particularly in view of the value of carnitine in the prevention of cell aging.

[Vitamin C in children with trisomy 21]. / Vitamina C in bambini affetti da trisomia 21.

The present study revealed ascorbic acid deficiency in the blood of many children with Down's syndrome. It also revealed a fairly definite connection between Vitamin C deficiency and diet in these patients and a similar link between ascorbic acid deficiency and this incidence of infections. Where necessary the prescription of Vitamin C for the prevention and treatment of recurring infection is therefore recommended, bearing in mind the valuable antioxidant properties of ascorbic acid that can be exploited in combating cell deterioration.

[The immunological profile of children with Down's syndrome]. / Il profilo immunologico dei bambini Down.

In 1965 Benda demonstrated that bioptic and autoptic material of children with Down's syndrome showed hypoplasia of the thymus with poor histological differentiation between the cortex and medulla and impairment of Hassal's corpuscles which were also fewer than normal. In the seventies studies revealed the increased susceptibility to infections and higher incidence of leucosis in Down's syndrome patients as well as changes of immunologic defences (in particular cell mediated immunity). This study examines 35 children (16 boys and 19 girls) aged 6 months-20 years. Subjects were divided into a group of 18 cases in poor health with a history of recurrent infections and a group of 17 children in good health. Skin tests were performed by inoculating 0.1 ml of a solution formed by 1 ml physiological solution and 0.1 ml tetanus toxoid. Skin reaction was evaluated 48 hours later. Lymphocyte typing tests were performed with the rosette method and with monoclonal antibodies for T lymphocytes and with the determination of surface immunoglobulins for B lymphocytes. OKT4 (T helper), OKT8 (T suppressor) subsets assayed and the OKT4/OKT8 ratio was determined. Skin tests were negative in 3 cases (8.6%). The number of B lymphocytes was normal in all children. Total number of lymphocytes was decreased in 51.4% of cases. Two subjects had a reduction of OKT4 and 14 had an increased of OKT8 and 16 a significantly lower OKT4/OKT8 ratio. It is clear that skin tests were normal also in those children with low total lymphocyte values. The most closely related parameter to mobility was the OKT4/OKT8 ratio and the most distantly related on was the skin test. Only 3 cases had modifications of all 3 parameters together. Apart from the constant and complete immunological deficit described by many authors and which we cannot confirm the results of this study are in agreement with those of other authors.