Background The ketogenic diet is a high fat, adequate protein, low carbohydrate diet. It has been... more Background The ketogenic diet is a high fat, adequate protein, low carbohydrate diet. It has been used in the treatment of intractable childhood epilepsy, difficult-to-control seizures in adults, GLUT1 deficiency syndrome and PDH deficiency. conclusions This review traces a history of ketogenic diet, reviews its uses and side effects, and discusses possible alternatives and the dietćs possible mechanisms of action. We show how to use the diet in practice. Protocol and calculations are presented. We look toward possible future uses of the ketogenic diet, since it is efficient, under doctorćs supervison safe, but very demanding, additional treatment.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics, 2008
Infants with severe cardiorespiratory failure treated with extracorporeal membrane oxygenation ar... more Infants with severe cardiorespiratory failure treated with extracorporeal membrane oxygenation are at risk of hypoxic-ischemic injury and infarction of the brain, intracranial hemorrhage, and seizures. Consequently, this can lead to adverse neurodevelopmental outcome. We present a neonate treated with veno-arterial extracorporeal membrane oxygenation due to diaphragmatic hernia. The infant's brain function was continuously monitored with amplitude-integrated electroencephalography. The child experienced clinical seizures and subclinical seizure discharges, detected by amplitude-integrated electroencephalography, permitting the opportunity to treat them and adjust the anticonvulsive treatment accordingly.
Joubert syndrome (JS) is a recessive ciliopathy characterised by a distinctive brain malformation... more Joubert syndrome (JS) is a recessive ciliopathy characterised by a distinctive brain malformation 'the molar tooth sign'. Mutations in >27 genes cause JS, and mutations in 12 of these genes also cause Meckel-Gruber syndrome (MKS). The goals of this work are to describe the clinical features of MKS1-related JS and determine whether disease causing MKS1 mutations affect cellular phenotypes such as cilium number, length and protein content as potential mechanisms underlying JS. We measured cilium number, length and protein content (ARL13B and INPP5E) by immunofluorescence in fibroblasts from individuals with MKS1-related JS and in a three-dimensional (3D) spheroid rescue assay to test the effects of disease-related MKS1 mutations. We report MKS1 mutations (eight of them previously unreported) in nine individuals with JS. A minority of the individuals with MKS1-related JS have MKS features. In contrast to the truncating mutations associated with MKS, all of the individuals wi...
Indiplon is a short-acting hypnotic that is currently being developed as a treatment for insomnia... more Indiplon is a short-acting hypnotic that is currently being developed as a treatment for insomnia by Neurocrine Biosciences and Pfizer, and is expected to be marketed in mid-2006. It is a high-affinity allosteric potentiator of GABAA responses that demonstrates preference for alpha1 subunit-containing GABAA receptors. Indiplon will be an addition to the general category of newer-generation hypnotics that now includes zaleplon, zolpidem, zopiclone and eszopiclone. Clinical trials were carried out with an immediate-release capsule and a modified-release tablet and demonstrate very positive efficacy and safety profiles. The major challenge will be developing a commercial success in the crowded insomnia treatment marketplace.
Vrednosti težkih kovin v krvi in specifičnih porfirinov v urinu pri otrocih z avtizmom Heavy meta... more Vrednosti težkih kovin v krvi in specifičnih porfirinov v urinu pri otrocih z avtizmom Heavy metals and specific porphyrine levels in children with autism Izvleček Izhodišča: Namen naše študije je bil primerjati skupino otrok s spektroavtističnimi motnjami (SAM) in kontrolno skupino otrok z drugimi nevrološkimi motnjami/boleznimi glede krvnih vrednosti težkih kovin (cink, baker, aluminij, živo srebro, svinec) in vrednosti specifičnih por-firinov v urinu. Metode: V študijo smo vključili skupino otrok s SAM (n = 52, povprečna starost = 6,2 let) in kontrolno skupino otrok z drugimi nevrološki-mi motnjami/boleznimi (n = 22, povprečna sta-rost = 6,6 let), ki sta bili med seboj primerljivi glede na razvojno starost oz. spoznavne sposob-nosti (Mann-Whitney U = 565.0, p = .595). Me-ritve težkih kovin v krvi smo izvedli z atomsko absorbcijsko spektrometrijo, meritve porfirinov v urinu pa z metodo HPLC s fluorimetričnim detektorjem. Pri analizi rezultatov smo uporabili večsmerno analizo kovar...
Differential diagnosis in a newborn with dysmorphic features and profound neurologic dysfunction ... more Differential diagnosis in a newborn with dysmorphic features and profound neurologic dysfunction should include the cerebro-hepato-renal syndrome of Zellweger. Its distinct clinical features, markedly elevated plasma levels of very long chain fatty acids and characteristic radiological findings support the diagnosis, which can now be confirmed by genetic markers. Quite consistent abnormalities of the neurophysiological studies in this syndrome have also been reported. We report a case with typical clinical and biochemical findings in whom distinctive brain MRI abnormalities were found. The results of neurophysiological studies with an unusual EEG pattern of continuous negative vertex sharp waves and spikes are discussed. We believe that such a pattern could be considered as a pathognomonic EEG finding, especially in cases of Zellweger syndrome with extensive brain abnormalities and may even be closely associated with cortical dysplasias.
International review of psychiatry (Abingdon, England), 2014
Advances in understanding the neurochemistry of sleep and waking have stimulated new pharmacologi... more Advances in understanding the neurochemistry of sleep and waking have stimulated new pharmacological directions in the treatment of insomnia. While the sedation of historic insomnia medications was discovered serendipitously, now compounds can be developed for specific molecular targets with known sleep-related actions. Numerous investigational compounds, including some entirely novel approaches, are being evaluated currently as possible insomnia treatments. In recent years the US Federal Drug Administration (FDA) has approved medications with new pharmacodynamic and pharmacokinetic properties thereby extending the options for personalized pharmacotherapy. The FDA is reviewing new applications for innovative sleep-promoting medications currently, including suvorexant and tasimelteon. Presently the FDA-approved insomnia treatment medications include benzodiazepine receptor agonists available in immediate-release, extended-release, and alternative delivery oral absorption formulations...
This article reviews the recently Food and Drug Administrationapproved sleep-promoting medication... more This article reviews the recently Food and Drug Administrationapproved sleep-promoting medications as well as new compounds being investigated as possible future insomnia treatments. The new medications indicated for the treatment of insomnia include significant advances in pharmacokinetic and pharmacodynamic approaches. All approved sleep-promoting medications are indicated for difficulties with sleep onset and some have an additional indication for sleep maintenance. The recently approved insomnia medications no longer have an implied restriction on their duration of use. There is now a controlled-release formulation of a benzodiazepine receptor agonist, as well as a selective melatonin receptor agonist. New potential pharmacologic targets for treating insomnia have become evident, with advances in the understanding of the neural mechanisms regulating the sleep-wake cycle. Currently being evaluated are a wide range of compounds that modulate γ-aminobutyric acid, histamine, serotonin, melatonin, adenosine, corticotrophin-releasing factor, and hypocretin/orexin systems. Needs Assessment: Three new medications recently have been approved Needs Assessment: Three new medications recently have been approved Needs Assessment: This activity has been peer-reviewed and approved by Eric Hollander, MD, chair at Mount Sinai School of Medicine. Review
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics, 2008
Infants with severe cardiorespiratory failure treated with extracorporeal membrane oxygenation ar... more Infants with severe cardiorespiratory failure treated with extracorporeal membrane oxygenation are at risk of hypoxic-ischemic injury and infarction of the brain, intracranial hemorrhage, and seizures. Consequently, this can lead to adverse neurodevelopmental outcome. We present a neonate treated with veno-arterial extracorporeal membrane oxygenation due to diaphragmatic hernia. The infant's brain function was continuously monitored with amplitude-integrated electroencephalography. The child experienced clinical seizures and subclinical seizure discharges, detected by amplitude-integrated electroencephalography, permitting the opportunity to treat them and adjust the anticonvulsive treatment accordingly.
Insomnia is a common problem in the general population and has a higher prevalence in persons wit... more Insomnia is a common problem in the general population and has a higher prevalence in persons with medical and psychiatric disorders. Although insomnia is most often transient, occurring as a result of identifiable stressors, a substantial portion of insomnia cases involve persistent sleep difficulty. This chronic form of insomnia may be associated with a wide range of adverse consequences. An understanding of the characteristics and causes of this disorder and the available therapeutic strategies will promote more effective identification and treatment of patients with chronic insomnia.
This study was performed with the aim of determining the diagnostic profile of newborns with hypo... more This study was performed with the aim of determining the diagnostic profile of newborns with hypotonia and of analyzing the usefulness of different procedures in the diagnostic process. One hundred thirty-eight hypotonic newborns were identified through the search of hospital records in a 10-year period: 121 (88%) had central hypotonia and 13 (9%) had peripheral hypotonia, whereas 4 (3%) remained unclassified. Analysis of the contribution of clinical data and results of investigations led to the construction of an algorithm, by which all cases in the group were diagnosed. Step 1, which included clinical data and results of examinations, solved 50% of all diagnosed cases. Neuroimaging techniques made up step 2 and contributed to the diagnosis in 13%. Step 3 was accomplished by a search through Oxford Medical Databases, which yielded the final diagnosis in 9%, whereas karyotyping and fluorescent in situ hybridization for Prader-Willi syndrome comprised step 4 and contributed to the di...
Insomnia is a common problem that for many sufferers persists chronically and may result from a w... more Insomnia is a common problem that for many sufferers persists chronically and may result from a wide range of causes. Specific treatments address particular underlying medical disorders. General therapeutic approaches, including pharmacologic and behavioral strategies, may have broad applicability to insomnia patients. Many different medications and substances have been used in an attempt to improve sleep. This article reviews the advantages and disadvantages of medications and other substances employed to promote improved sleep. Special emphasis is given to the use of the newer-generation benzodiazepine receptor agonist hypnotics.
Deafness TBC1D24 gene Early-onset epileptic encephalopathy a b s t r a c t Background: Recent stu... more Deafness TBC1D24 gene Early-onset epileptic encephalopathy a b s t r a c t Background: Recent studies have shown that recessive mutations in the TBC1D24 gene cause a variety of epilepsy syndromes, DOORS syndrome and nonsyndromic deafness. Methods/Results: We report on two siblings with hypotonia, early-onset epileptic encephalopathy, and severe developmental delay. The patients presented with clonic and myoclonic jerks within 1 h after birth. The seizures were resistant to treatment. Audiologic examination showed bilateral sensorineural hearing loss in both siblings. Genetic analysis revealed compound heterozygous mutations in the TBC1D24 gene: a novel missense mutation c.32A > G (p.Asp11Gly) in exon 2 and a frameshift mutation c.1008delT (p.His336Glnfs*12) in exon 4.
Background. Myotonic dystrophy is inherited as an autosomal dominant trait. It is characterized b... more Background. Myotonic dystrophy is inherited as an autosomal dominant trait. It is characterized by myoto- nia, myopathy of voluntary and involuntary muscles, frontal baldness in men, cardiac conduction abnormalities, catha- racts, intellectual deterioration and endocrinopathy. Men with this disorder have often gonadal atrophy and infertility. On the other hand women are generally fertile. During pregnancy their myopathy worsens, often causing
BACKGROUND: Microcephaly-capillary malformation syndrome is a newly described neurocutaneous enti... more BACKGROUND: Microcephaly-capillary malformation syndrome is a newly described neurocutaneous entity that is characterized by congenital and progressive microcephaly, intractable epilepsy, profound developmental delay, multiple small capillary malformations on the skin, and poor somatic growth. Recently, mutations in the STAMBP gene have been identified as causative in the pathogenesis of this syndrome. PATIENTS: We describe two brothers (ages 7 and 12 years) from consanguineous parents of Saudi ancestry. Along with the established main clinical features of this syndrome, these boys exhibited certain novel and distinctive phenotypic features (congenital hypothyroidism and autistic-like behavior with intermittent repetitive hand-flapping movements). Genetic studies revealed the presence of homozygous pathogenic STAMPB mutation. CONCLUSION: This report presents the longest follow-up of patients with microcephaly-capillary syndrome so far reported and emphasize the syndrome's phenotype variability.
Benign paroxysmal torticollis is probably an under-diagnosed condition of infancy. It is a self-l... more Benign paroxysmal torticollis is probably an under-diagnosed condition of infancy. It is a self-limiting disorder characterised by periods of unusual, sustained posture of the head and neck, during which the head tilts to one side. Episodes are often accompanied by marked autonomic features, irritability, ataxia, apathy and drowsiness. They last several hours to a few days and are often recurring every few weeks. They subside within the pre-school years; however, during later childhood, there is a tendency to develop migraine. Three cases of benign paroxysmal torticollis are presented and are compared with cases in the literature. A telephone survey has been conducted to determine what is the general awareness of paediatricians of this condition in Cyprus. Eighty-two paediatricians were randomly selected out of 235 paediatricians. All of them agreed to participate. Our cases revealed that benign paroxysmal torticollis may coexist with other problems during infancy. The telephone survey showed that only two out of eighty-two (2.4%) of the paediatricians are aware of the condition, and none of them was confident regarding the management. Our telephone survey clearly shows that Cypriot paediatricians are not familiar with benign paroxysmal torticollis in infancy which is a benign, self-limiting disorder. It is essential to recognise the condition and to reassure parents of its benign course and not to be misdiagnosed for other disorders, such as epileptic seizures. We have shown again that benign paroxysmal torticollis in infancy may coexist with motor delay and hearing problems.
We evaluated the functional outcome in a cohort of 22 children with mitochondrial diseases. The P... more We evaluated the functional outcome in a cohort of 22 children with mitochondrial diseases. The Pediatric Evaluation of Disability Inventory was administered and scaled scores determined. A large variability in functional skills was seen in all 3 assessed domains: Self-Care (46.4 ± 25.6 S.D.; median 42.4; range 11.8-100), Mobility (47.1 ± 30.4 S.D.; median 46.7; range 6.1-100), and Social Function (49.7 ± 22.3 S.D.; median 45.6; range 21.6-100). There was also a large variability in caregiver assistance, ranging from independent functioning to total dependence on assistance for the following: Self-Care (29.0 ± 33.7 S.D.; median 10.1; range 0-100), Mobility (36.6 ± 38.5 S.D.; median 26.1; range 0-100), and Social Function (42.9 ± 32.4 S.D.; median 44.4; range 0-100). The Pediatric Evaluation of Disability Inventory scores describe in depth different, but strongly related, aspects of everyday functioning in children with mitochondrial diseases. The importance of caregiver assistance in helping these children should not be underestimated. The use of assistive devices was estimated, which were found to be used by few patients. Ó 2011 Elsevier Inc. All rights reserved. Rogac M, Meznaric M, Zeviani M, Sperl W, Neubauer D. Functional outcome of children with mitochondrial diseases. Pediatr Neurol 2011;44:340-346.
Background The ketogenic diet is a high fat, adequate protein, low carbohydrate diet. It has been... more Background The ketogenic diet is a high fat, adequate protein, low carbohydrate diet. It has been used in the treatment of intractable childhood epilepsy, difficult-to-control seizures in adults, GLUT1 deficiency syndrome and PDH deficiency. conclusions This review traces a history of ketogenic diet, reviews its uses and side effects, and discusses possible alternatives and the dietćs possible mechanisms of action. We show how to use the diet in practice. Protocol and calculations are presented. We look toward possible future uses of the ketogenic diet, since it is efficient, under doctorćs supervison safe, but very demanding, additional treatment.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics, 2008
Infants with severe cardiorespiratory failure treated with extracorporeal membrane oxygenation ar... more Infants with severe cardiorespiratory failure treated with extracorporeal membrane oxygenation are at risk of hypoxic-ischemic injury and infarction of the brain, intracranial hemorrhage, and seizures. Consequently, this can lead to adverse neurodevelopmental outcome. We present a neonate treated with veno-arterial extracorporeal membrane oxygenation due to diaphragmatic hernia. The infant's brain function was continuously monitored with amplitude-integrated electroencephalography. The child experienced clinical seizures and subclinical seizure discharges, detected by amplitude-integrated electroencephalography, permitting the opportunity to treat them and adjust the anticonvulsive treatment accordingly.
Joubert syndrome (JS) is a recessive ciliopathy characterised by a distinctive brain malformation... more Joubert syndrome (JS) is a recessive ciliopathy characterised by a distinctive brain malformation 'the molar tooth sign'. Mutations in >27 genes cause JS, and mutations in 12 of these genes also cause Meckel-Gruber syndrome (MKS). The goals of this work are to describe the clinical features of MKS1-related JS and determine whether disease causing MKS1 mutations affect cellular phenotypes such as cilium number, length and protein content as potential mechanisms underlying JS. We measured cilium number, length and protein content (ARL13B and INPP5E) by immunofluorescence in fibroblasts from individuals with MKS1-related JS and in a three-dimensional (3D) spheroid rescue assay to test the effects of disease-related MKS1 mutations. We report MKS1 mutations (eight of them previously unreported) in nine individuals with JS. A minority of the individuals with MKS1-related JS have MKS features. In contrast to the truncating mutations associated with MKS, all of the individuals wi...
Indiplon is a short-acting hypnotic that is currently being developed as a treatment for insomnia... more Indiplon is a short-acting hypnotic that is currently being developed as a treatment for insomnia by Neurocrine Biosciences and Pfizer, and is expected to be marketed in mid-2006. It is a high-affinity allosteric potentiator of GABAA responses that demonstrates preference for alpha1 subunit-containing GABAA receptors. Indiplon will be an addition to the general category of newer-generation hypnotics that now includes zaleplon, zolpidem, zopiclone and eszopiclone. Clinical trials were carried out with an immediate-release capsule and a modified-release tablet and demonstrate very positive efficacy and safety profiles. The major challenge will be developing a commercial success in the crowded insomnia treatment marketplace.
Vrednosti težkih kovin v krvi in specifičnih porfirinov v urinu pri otrocih z avtizmom Heavy meta... more Vrednosti težkih kovin v krvi in specifičnih porfirinov v urinu pri otrocih z avtizmom Heavy metals and specific porphyrine levels in children with autism Izvleček Izhodišča: Namen naše študije je bil primerjati skupino otrok s spektroavtističnimi motnjami (SAM) in kontrolno skupino otrok z drugimi nevrološkimi motnjami/boleznimi glede krvnih vrednosti težkih kovin (cink, baker, aluminij, živo srebro, svinec) in vrednosti specifičnih por-firinov v urinu. Metode: V študijo smo vključili skupino otrok s SAM (n = 52, povprečna starost = 6,2 let) in kontrolno skupino otrok z drugimi nevrološki-mi motnjami/boleznimi (n = 22, povprečna sta-rost = 6,6 let), ki sta bili med seboj primerljivi glede na razvojno starost oz. spoznavne sposob-nosti (Mann-Whitney U = 565.0, p = .595). Me-ritve težkih kovin v krvi smo izvedli z atomsko absorbcijsko spektrometrijo, meritve porfirinov v urinu pa z metodo HPLC s fluorimetričnim detektorjem. Pri analizi rezultatov smo uporabili večsmerno analizo kovar...
Differential diagnosis in a newborn with dysmorphic features and profound neurologic dysfunction ... more Differential diagnosis in a newborn with dysmorphic features and profound neurologic dysfunction should include the cerebro-hepato-renal syndrome of Zellweger. Its distinct clinical features, markedly elevated plasma levels of very long chain fatty acids and characteristic radiological findings support the diagnosis, which can now be confirmed by genetic markers. Quite consistent abnormalities of the neurophysiological studies in this syndrome have also been reported. We report a case with typical clinical and biochemical findings in whom distinctive brain MRI abnormalities were found. The results of neurophysiological studies with an unusual EEG pattern of continuous negative vertex sharp waves and spikes are discussed. We believe that such a pattern could be considered as a pathognomonic EEG finding, especially in cases of Zellweger syndrome with extensive brain abnormalities and may even be closely associated with cortical dysplasias.
International review of psychiatry (Abingdon, England), 2014
Advances in understanding the neurochemistry of sleep and waking have stimulated new pharmacologi... more Advances in understanding the neurochemistry of sleep and waking have stimulated new pharmacological directions in the treatment of insomnia. While the sedation of historic insomnia medications was discovered serendipitously, now compounds can be developed for specific molecular targets with known sleep-related actions. Numerous investigational compounds, including some entirely novel approaches, are being evaluated currently as possible insomnia treatments. In recent years the US Federal Drug Administration (FDA) has approved medications with new pharmacodynamic and pharmacokinetic properties thereby extending the options for personalized pharmacotherapy. The FDA is reviewing new applications for innovative sleep-promoting medications currently, including suvorexant and tasimelteon. Presently the FDA-approved insomnia treatment medications include benzodiazepine receptor agonists available in immediate-release, extended-release, and alternative delivery oral absorption formulations...
This article reviews the recently Food and Drug Administrationapproved sleep-promoting medication... more This article reviews the recently Food and Drug Administrationapproved sleep-promoting medications as well as new compounds being investigated as possible future insomnia treatments. The new medications indicated for the treatment of insomnia include significant advances in pharmacokinetic and pharmacodynamic approaches. All approved sleep-promoting medications are indicated for difficulties with sleep onset and some have an additional indication for sleep maintenance. The recently approved insomnia medications no longer have an implied restriction on their duration of use. There is now a controlled-release formulation of a benzodiazepine receptor agonist, as well as a selective melatonin receptor agonist. New potential pharmacologic targets for treating insomnia have become evident, with advances in the understanding of the neural mechanisms regulating the sleep-wake cycle. Currently being evaluated are a wide range of compounds that modulate γ-aminobutyric acid, histamine, serotonin, melatonin, adenosine, corticotrophin-releasing factor, and hypocretin/orexin systems. Needs Assessment: Three new medications recently have been approved Needs Assessment: Three new medications recently have been approved Needs Assessment: This activity has been peer-reviewed and approved by Eric Hollander, MD, chair at Mount Sinai School of Medicine. Review
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics, 2008
Infants with severe cardiorespiratory failure treated with extracorporeal membrane oxygenation ar... more Infants with severe cardiorespiratory failure treated with extracorporeal membrane oxygenation are at risk of hypoxic-ischemic injury and infarction of the brain, intracranial hemorrhage, and seizures. Consequently, this can lead to adverse neurodevelopmental outcome. We present a neonate treated with veno-arterial extracorporeal membrane oxygenation due to diaphragmatic hernia. The infant's brain function was continuously monitored with amplitude-integrated electroencephalography. The child experienced clinical seizures and subclinical seizure discharges, detected by amplitude-integrated electroencephalography, permitting the opportunity to treat them and adjust the anticonvulsive treatment accordingly.
Insomnia is a common problem in the general population and has a higher prevalence in persons wit... more Insomnia is a common problem in the general population and has a higher prevalence in persons with medical and psychiatric disorders. Although insomnia is most often transient, occurring as a result of identifiable stressors, a substantial portion of insomnia cases involve persistent sleep difficulty. This chronic form of insomnia may be associated with a wide range of adverse consequences. An understanding of the characteristics and causes of this disorder and the available therapeutic strategies will promote more effective identification and treatment of patients with chronic insomnia.
This study was performed with the aim of determining the diagnostic profile of newborns with hypo... more This study was performed with the aim of determining the diagnostic profile of newborns with hypotonia and of analyzing the usefulness of different procedures in the diagnostic process. One hundred thirty-eight hypotonic newborns were identified through the search of hospital records in a 10-year period: 121 (88%) had central hypotonia and 13 (9%) had peripheral hypotonia, whereas 4 (3%) remained unclassified. Analysis of the contribution of clinical data and results of investigations led to the construction of an algorithm, by which all cases in the group were diagnosed. Step 1, which included clinical data and results of examinations, solved 50% of all diagnosed cases. Neuroimaging techniques made up step 2 and contributed to the diagnosis in 13%. Step 3 was accomplished by a search through Oxford Medical Databases, which yielded the final diagnosis in 9%, whereas karyotyping and fluorescent in situ hybridization for Prader-Willi syndrome comprised step 4 and contributed to the di...
Insomnia is a common problem that for many sufferers persists chronically and may result from a w... more Insomnia is a common problem that for many sufferers persists chronically and may result from a wide range of causes. Specific treatments address particular underlying medical disorders. General therapeutic approaches, including pharmacologic and behavioral strategies, may have broad applicability to insomnia patients. Many different medications and substances have been used in an attempt to improve sleep. This article reviews the advantages and disadvantages of medications and other substances employed to promote improved sleep. Special emphasis is given to the use of the newer-generation benzodiazepine receptor agonist hypnotics.
Deafness TBC1D24 gene Early-onset epileptic encephalopathy a b s t r a c t Background: Recent stu... more Deafness TBC1D24 gene Early-onset epileptic encephalopathy a b s t r a c t Background: Recent studies have shown that recessive mutations in the TBC1D24 gene cause a variety of epilepsy syndromes, DOORS syndrome and nonsyndromic deafness. Methods/Results: We report on two siblings with hypotonia, early-onset epileptic encephalopathy, and severe developmental delay. The patients presented with clonic and myoclonic jerks within 1 h after birth. The seizures were resistant to treatment. Audiologic examination showed bilateral sensorineural hearing loss in both siblings. Genetic analysis revealed compound heterozygous mutations in the TBC1D24 gene: a novel missense mutation c.32A > G (p.Asp11Gly) in exon 2 and a frameshift mutation c.1008delT (p.His336Glnfs*12) in exon 4.
Background. Myotonic dystrophy is inherited as an autosomal dominant trait. It is characterized b... more Background. Myotonic dystrophy is inherited as an autosomal dominant trait. It is characterized by myoto- nia, myopathy of voluntary and involuntary muscles, frontal baldness in men, cardiac conduction abnormalities, catha- racts, intellectual deterioration and endocrinopathy. Men with this disorder have often gonadal atrophy and infertility. On the other hand women are generally fertile. During pregnancy their myopathy worsens, often causing
BACKGROUND: Microcephaly-capillary malformation syndrome is a newly described neurocutaneous enti... more BACKGROUND: Microcephaly-capillary malformation syndrome is a newly described neurocutaneous entity that is characterized by congenital and progressive microcephaly, intractable epilepsy, profound developmental delay, multiple small capillary malformations on the skin, and poor somatic growth. Recently, mutations in the STAMBP gene have been identified as causative in the pathogenesis of this syndrome. PATIENTS: We describe two brothers (ages 7 and 12 years) from consanguineous parents of Saudi ancestry. Along with the established main clinical features of this syndrome, these boys exhibited certain novel and distinctive phenotypic features (congenital hypothyroidism and autistic-like behavior with intermittent repetitive hand-flapping movements). Genetic studies revealed the presence of homozygous pathogenic STAMPB mutation. CONCLUSION: This report presents the longest follow-up of patients with microcephaly-capillary syndrome so far reported and emphasize the syndrome's phenotype variability.
Benign paroxysmal torticollis is probably an under-diagnosed condition of infancy. It is a self-l... more Benign paroxysmal torticollis is probably an under-diagnosed condition of infancy. It is a self-limiting disorder characterised by periods of unusual, sustained posture of the head and neck, during which the head tilts to one side. Episodes are often accompanied by marked autonomic features, irritability, ataxia, apathy and drowsiness. They last several hours to a few days and are often recurring every few weeks. They subside within the pre-school years; however, during later childhood, there is a tendency to develop migraine. Three cases of benign paroxysmal torticollis are presented and are compared with cases in the literature. A telephone survey has been conducted to determine what is the general awareness of paediatricians of this condition in Cyprus. Eighty-two paediatricians were randomly selected out of 235 paediatricians. All of them agreed to participate. Our cases revealed that benign paroxysmal torticollis may coexist with other problems during infancy. The telephone survey showed that only two out of eighty-two (2.4%) of the paediatricians are aware of the condition, and none of them was confident regarding the management. Our telephone survey clearly shows that Cypriot paediatricians are not familiar with benign paroxysmal torticollis in infancy which is a benign, self-limiting disorder. It is essential to recognise the condition and to reassure parents of its benign course and not to be misdiagnosed for other disorders, such as epileptic seizures. We have shown again that benign paroxysmal torticollis in infancy may coexist with motor delay and hearing problems.
We evaluated the functional outcome in a cohort of 22 children with mitochondrial diseases. The P... more We evaluated the functional outcome in a cohort of 22 children with mitochondrial diseases. The Pediatric Evaluation of Disability Inventory was administered and scaled scores determined. A large variability in functional skills was seen in all 3 assessed domains: Self-Care (46.4 ± 25.6 S.D.; median 42.4; range 11.8-100), Mobility (47.1 ± 30.4 S.D.; median 46.7; range 6.1-100), and Social Function (49.7 ± 22.3 S.D.; median 45.6; range 21.6-100). There was also a large variability in caregiver assistance, ranging from independent functioning to total dependence on assistance for the following: Self-Care (29.0 ± 33.7 S.D.; median 10.1; range 0-100), Mobility (36.6 ± 38.5 S.D.; median 26.1; range 0-100), and Social Function (42.9 ± 32.4 S.D.; median 44.4; range 0-100). The Pediatric Evaluation of Disability Inventory scores describe in depth different, but strongly related, aspects of everyday functioning in children with mitochondrial diseases. The importance of caregiver assistance in helping these children should not be underestimated. The use of assistive devices was estimated, which were found to be used by few patients. Ó 2011 Elsevier Inc. All rights reserved. Rogac M, Meznaric M, Zeviani M, Sperl W, Neubauer D. Functional outcome of children with mitochondrial diseases. Pediatr Neurol 2011;44:340-346.
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