Utility of Whole Exome Sequencing for Genetic Diagnosis of Previously Undiagnosed Pediatric Neurology Patients.

Whole exome sequencing enables scanning a large number of genes for relatively low costs. The authors investigate its use for previously undiagnosed pediatric neurological patients. This retrospective cohort study performed whole exome sequencing on 57 patients of "Magen" neurogenetic clinics, with unknown diagnoses despite previous workup. The authors report on clinical features, causative genes, and treatment modifications and provide an analysis of whole exome sequencing utility per primary clinical feature. A causative gene was identified in 49.1% of patients, of which 17 had an autosomal dominant mutation, 9 autosomal recessive, and 2 X-linked. The highest rate of positive diagnosis was found for patients with developmental delay, ataxia, or suspected neuromuscular disease. Whole exome sequencing warranted a definitive change of treatment for 5 patients. Genetic databases were updated accordingly. In conclusion, whole exome sequencing is useful in obtaining a high detection rate for previously undiagnosed disorders. Use of this technique could affect diagnosis, treatment, and prognostics for both patients and relatives.

Effect of high-dose glucocorticosteroid treatment for infantile spasms on quantitative bone parameters later in life.

This study evaluated possible long-term effects of prolonged high-dose glucocorticosteroid administration in infancy. Thirty patients (16 male, 14 female; age 4.8-33 years) who had completed treatment with adrenocorticotropic hormone (ACTH) followed by glucocorticoids for infantile spasms at a tertiary pediatric hospital at least 2 years previously were invited to undergo quantitative bone ultrasound. The mean speed of soundZ score was -1.085 ± 1.079 for the radius and -0.22 ± 1.19 for the tibia on the nondominant side (P = .0022). The difference from the reference mean (0) was statistically significant for the radius (P < .001). There were no significant differences in radial or tibial mean speed of soundZ scores by age (prepubertal versus pubertal/postpubertal). In conclusion, a high percentage of patients treated with glucocorticoids for infantile spasms have a low radial speed of soundZ score later in life. Long-term follow-up can help to prevent and treat impairments in bone density, especially in non-weight-bearing organs.