[FROM GENETICS OF FRAGILE X SYNDROME TO DEVELOPMENT OF TARGETED AND PERSONALIZED DRUG THERAPY].

INTRODUCTION: At the end of the last century Fragile X syndrome was identified, and the main syndrome characteristics were discovered. The syndrome is caused from a flaw in the number of nucleotide repeats that encodes for a regulatory protein which is critical for neural connectivity and normal brain development. The syndrome is characterized by neurodevelopmental and intellectual disabilities, autism spectrum features and other clinical features associated with the same gene aberration. The number of trinucleotide repeats have a direct effect on the outcome and the need for genetic counseling. We advocate performing genetic tests for every child with developmental delay, learning disabilities, autism spectrum disorders and especially, intellectual impairment. It is also advisable to check the number of nucleotide repeats of the gene, in every woman suffering from infertility or early menopause. In addition, genetic testing should be performed on older adults manifesting early symptoms of Parkinson's disease, balance instability, tremor or cognitive dysfunction with unknown etiology. Due to the tremendous progress in understanding the biological mechanisms of the syndrome, new molecules/drugs have been proposed and are tested, in order to find a way to bypass the defect mechanism underlying the disorder. We will review the most commonly used drugs in the treatment of Fragile X syndrome and many medications that are currently under investigation as a more targeted treatment.

Inadequate asthma treatment practices and noncompliance in Israel.

Childhood asthma morbidity and mortality are increasing despite improvements in asthma therapy. The changes over the past decade in the guidelines for treatment of children with severe asthma have led to a reduction in admissions and readmissions to the pediatric intensive care unit (PICU). The Israeli medical infrastructure is exemplary in its capability of extending appropriate medical services to its entire population. Our objective was to look at the background of preventive maintenance treatment and treatment during an acute episode in children admitted to PICUs with severe asthma, and to identify areas that could be targeted for change. A 5-year retrospective chart audit on acute asthma admissions was conducted in two PICUs of general community hospitals representative of the provision of medical care in Israel. The prehospitalization preventive management and acute treatment prior to PICU admission were evaluated, and the number of admissions and readmissions was recorded. The index admission was the first episode of acute asthma for only 3% of the children: 25% of patients required readmission, and 15% of these to the PICU. In spite of a proven history of acute exacerbations of the disease, only 60% were on continuous treatment between attacks, and 29% of them had abruptly discontinued treatment, most of them shortly before the onset of the index attack. Inhaled steroids were used as maintenance and preventive treatment by less than one-third of the children, with the other two-thirds receiving mainly beta-2 agonists drugs. In conclusion, an unacceptably large proportion of asthmatic children do not receive the recommended maintenance and preventive treatment because of poor compliance, lack of education, or insufficient healthcare provision. This has probably led to avoidable recurrences of acute asthma exacerbations and unnecessary use of PICU facilities. These findings suggest that steps for implementing recommended guidelines and an educational program are needed.

Sporadic major hyperekplexia in neonates and infants: clinical manifestations and outcome.

The aim of the present study is to report on the syndrome of sporadic major hyperekplexia during the neonatal period and early infancy, diagnosed in 39 patients at an average age of 3.3 months, the most severely affected during the first month of life. The patients mainly presented with marked irritability and recurrent startles in response to handling or even minute sounds, accompanied by rhythmic jerky movements and occasionally breath-holding episodes. Family history was negative for hyperekplexia, although eight parents reported jerky leg movements during sleep. The hallmark of hyperekplexia consisted of a hyper-alert gaze and an exaggerated startle with delayed habituation, also elicited by nose tapping and air blowing on the face accompanied by increasing rigidity. Nine severely affected infants, presenting with relentless startles, marked stiffness, violent rhythmic jerks, and breath-holding episodes were treated with oral low doses of clonazepam and completely recovered. Overall, the debilitating symptoms of hyperekplexia gradually resolved in all 39 infants, and their developmental assessment by 2 years of age was within the normal range. Therefore a prompt diagnosis of hyperekplexia during the neonatal period and early infancy, and then treatment if required with benzodiazepines to alleviate the debilitating symptoms, may prevent life-threatening events and enable better feeding and handling. Establishing the diagnosis of such a relatively benign disorder with a favorable developmental outcome may avoid unjustified extensive investigations or unnecessary treatment, suspecting an ominous progressive neurologic disorder.