Volume 88 Number 2
Hearing loss in Noonan syndrome To the Editor: In recent reviews1-~ hearing loss is not mentioned as a feature of the Noonan syndrome. On the contrary, hearing loss is well known in Turner syndrome? HelleF' reported bilateral nerve deafness in one case of Noonan syndrome. Duenas 7 found hearing conduction deficit in three out of 25 cases. We recently studied two patients with Noonan syndrome with perceptive hearing loss and mental retardation. One patient is probably an autosomal dominant with paternal transmission. It has not been possible so far to study this family in more detail. Our experience is that the presence of hearing loss may not be detected for a long time in Noonan patients with mental retardation. In our opinion hearing loss could be an essential though not frequent feature o f the Noonan syndrome. C. Cremers Department of Human Genetics Faculty of Medicine University of Nijmegen Nijmegen, The Netherlands REFERENCES 1. Char F, et al: Birth Defects 8:110, 1972. 2. Summitt RL: in Bergsra D: Birth defects: Altas and compendium, Baltimore, 1973, The Williams & Wilkins Company. 3. Nora JJ, et al: Am J Dis Child 127:48, 1974. 4. Cremers CWRJ, and ter Haar BGA: Maandschr. Kindergeneesknnde, 42:322, 1974. 5. Anderson H, et ai: Acta Otolaryng Suppl 247, 1969. 6. Heller RH: J P~DIATR 66:48, t965. 7. Duenas DA, et al: South Med J 66:193, 1973.
Chronic versus intermittent phenobarbital therapy To the Editor: As pointed out by Ashes and associates ~in their recent article, there exists a wide variation in the diagnostic procedures performed and in the management of the first febrile seizure. Once the decision has been made to treat the patient prophylactically, it is important that the optimal mode of therapy be implemented by the physician. Melchoir and associates ~ demonstrated the ineffectiveness of phenytoin in the protection of children under three years of age from recurrent febrile seizures. Faero and associates, 3 utilizing continuous therapy and maintaining serum levels over 15 rag/liter of phenobarbital, have shown phenobarbital to be effective in protecting against recurrent febrile seizures. The controlled study by Millichap and associates 4 appears to be a focal point for the support of intermittent therapy over continuous therapy. They concluded that there was no difference in recurrence rate of febrile seizures between the two treatment
Letters to the Editor
363
groups and concluded that large doses of phenobarbital be administered at the first sign of illness. One cannot be certain that the children were in fact receiving the phenobarbital without serum level data which were not included in Millichap and associates' article. Svensmark and BuchthaF showed that even with double the ordinary dose of phenobarbital, one cannot achieve adequate blood levels in less than two to three days. It may take several weeks on ordinary doses to reach a steady-state level. In addition, there seems to be a delay in peak serum level of 12 to 18 hours after an oral dose of phenobarbital? Livingston has found that simple febrile seizures occur two to six hours after the onset of fever and rarely begin later than 24 hours. ~ On intermittent therapy, the parents assess the child and determine when treatment should begin. Mackintosh 8 found that, of the patients with a recurrent febrile seizure, five out of eight times the parents were unaware their child was pyrexic and in one other case the mother was unsure whether to begin therapy or not. Because a febrile seizure generally occurs within 48 hours after the onset of the fever, and because of the above mentioned problems in instituting therapy as well as reaching a therapeutic level after oral administration of phenobarbital, it seems very unlikely that intermittent therapy would be beneficial in the prevention of recurrent febrile seizures. If one decides to treat the child prophylactically, the treatment of choice should be continuous therapy with phenobarbital. In order to monitor compliance, the biggest problem encountered in chronic therapy," periodic blood levels should be drawn and should be maintained at a level o f at least 15 mg/ml. Richard L Sakai, Pharm.D. Post-Graduate Fellow in Pediatric Pharmacy State University o f New York Children's Hospital at Buffalo 219 Blyant St. Buffalo, N.Y. 14222 REFERENCES 1. Asnes RS, Hovick LF, Nealis J, et al: The first febrile seizure: a study of pediatric practice, J PEDIAXR 87:485, 1975. 2. Melchior JC, Buchthal F, and Lennox-Buchthal M: The ineffectivenesss o f diphenylhydantoin in preventing febrile convulsions in the age of greatest risk, under three years, Epilepsia 12:55, 1971. 3. Faero O, Kastrup KW, Lykkegaard E, et al: Successful prophylaxis of febrile convulsions with phenobarbital, Epilepsia 13:279, 1972. 4. Millichap JG, Akdort LM, and Madsen JA: A critical evaluation of therapy of febrile seizures, J PEDIATR 56:364, 1960. 5. Svensmark V, and Buchthal F: Accumulation of phenobarbital in man, Epilepsia 4:199, 1963. 6. Lous P: Plasma levels and urinary excretion of three barbituric acids after oral administration to man, Acta Pharmacol Toxicol 10:147, 1954. 7. Quellette EM: The child who convulses with fever, Pediatr Clin North Am 21:467, 1974. 8. Mackintosh TF: Studies on prophylactic treatment of febrile convulsions in children, Clin Pediatr 9:283, 1970.
Hearing loss in Noonan syndrome To the Editor: In recent reviews1-~ hearing loss is not mentioned as a feature of the Noonan syndrome. On the contrary, hearing loss is well known in Turner syndrome? HelleF' reported bilateral nerve deafness in one case of Noonan syndrome. Duenas 7 found hearing conduction deficit in three out of 25 cases. We recently studied two patients with Noonan syndrome with perceptive hearing loss and mental retardation. One patient is probably an autosomal dominant with paternal transmission. It has not been possible so far to study this family in more detail. Our experience is that the presence of hearing loss may not be detected for a long time in Noonan patients with mental retardation. In our opinion hearing loss could be an essential though not frequent feature o f the Noonan syndrome. C. Cremers Department of Human Genetics Faculty of Medicine University of Nijmegen Nijmegen, The Netherlands REFERENCES 1. Char F, et al: Birth Defects 8:110, 1972. 2. Summitt RL: in Bergsra D: Birth defects: Altas and compendium, Baltimore, 1973, The Williams & Wilkins Company. 3. Nora JJ, et al: Am J Dis Child 127:48, 1974. 4. Cremers CWRJ, and ter Haar BGA: Maandschr. Kindergeneesknnde, 42:322, 1974. 5. Anderson H, et ai: Acta Otolaryng Suppl 247, 1969. 6. Heller RH: J P~DIATR 66:48, t965. 7. Duenas DA, et al: South Med J 66:193, 1973.
Chronic versus intermittent phenobarbital therapy To the Editor: As pointed out by Ashes and associates ~in their recent article, there exists a wide variation in the diagnostic procedures performed and in the management of the first febrile seizure. Once the decision has been made to treat the patient prophylactically, it is important that the optimal mode of therapy be implemented by the physician. Melchoir and associates ~ demonstrated the ineffectiveness of phenytoin in the protection of children under three years of age from recurrent febrile seizures. Faero and associates, 3 utilizing continuous therapy and maintaining serum levels over 15 rag/liter of phenobarbital, have shown phenobarbital to be effective in protecting against recurrent febrile seizures. The controlled study by Millichap and associates 4 appears to be a focal point for the support of intermittent therapy over continuous therapy. They concluded that there was no difference in recurrence rate of febrile seizures between the two treatment
Letters to the Editor
363
groups and concluded that large doses of phenobarbital be administered at the first sign of illness. One cannot be certain that the children were in fact receiving the phenobarbital without serum level data which were not included in Millichap and associates' article. Svensmark and BuchthaF showed that even with double the ordinary dose of phenobarbital, one cannot achieve adequate blood levels in less than two to three days. It may take several weeks on ordinary doses to reach a steady-state level. In addition, there seems to be a delay in peak serum level of 12 to 18 hours after an oral dose of phenobarbital? Livingston has found that simple febrile seizures occur two to six hours after the onset of fever and rarely begin later than 24 hours. ~ On intermittent therapy, the parents assess the child and determine when treatment should begin. Mackintosh 8 found that, of the patients with a recurrent febrile seizure, five out of eight times the parents were unaware their child was pyrexic and in one other case the mother was unsure whether to begin therapy or not. Because a febrile seizure generally occurs within 48 hours after the onset of the fever, and because of the above mentioned problems in instituting therapy as well as reaching a therapeutic level after oral administration of phenobarbital, it seems very unlikely that intermittent therapy would be beneficial in the prevention of recurrent febrile seizures. If one decides to treat the child prophylactically, the treatment of choice should be continuous therapy with phenobarbital. In order to monitor compliance, the biggest problem encountered in chronic therapy," periodic blood levels should be drawn and should be maintained at a level o f at least 15 mg/ml. Richard L Sakai, Pharm.D. Post-Graduate Fellow in Pediatric Pharmacy State University o f New York Children's Hospital at Buffalo 219 Blyant St. Buffalo, N.Y. 14222 REFERENCES 1. Asnes RS, Hovick LF, Nealis J, et al: The first febrile seizure: a study of pediatric practice, J PEDIAXR 87:485, 1975. 2. Melchior JC, Buchthal F, and Lennox-Buchthal M: The ineffectivenesss o f diphenylhydantoin in preventing febrile convulsions in the age of greatest risk, under three years, Epilepsia 12:55, 1971. 3. Faero O, Kastrup KW, Lykkegaard E, et al: Successful prophylaxis of febrile convulsions with phenobarbital, Epilepsia 13:279, 1972. 4. Millichap JG, Akdort LM, and Madsen JA: A critical evaluation of therapy of febrile seizures, J PEDIATR 56:364, 1960. 5. Svensmark V, and Buchthal F: Accumulation of phenobarbital in man, Epilepsia 4:199, 1963. 6. Lous P: Plasma levels and urinary excretion of three barbituric acids after oral administration to man, Acta Pharmacol Toxicol 10:147, 1954. 7. Quellette EM: The child who convulses with fever, Pediatr Clin North Am 21:467, 1974. 8. Mackintosh TF: Studies on prophylactic treatment of febrile convulsions in children, Clin Pediatr 9:283, 1970.
