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Mohamad A Mikati - One of the best experts on this subject based on the ideXlab platform.
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hypothalamic pituitary dysfunction in Alternating Hemiplegia of childhood
European Journal of Paediatric Neurology, 2021Co-Authors: Keri Wallace, Lyndsey Prange, Elizabeth Greene, Mary E Moyamendez, Michael Freemark, Mohamad A MikatiAbstract:Abstract Background Many central nervous system disorders result in hypothalamic-pituitary (HP) axis dysfunction. Alternating Hemiplegia of Childhood (AHC) is usually caused by mutations in the ATP1A3 subunit of the Na+/K+ ATPase, predominantly affecting GABAergic interneurons. GABAergic interneurons and the ATP1A3 subunit are both important for function of the hypothalamus. However, whether HP dysfunction occurs in AHC and, if so, how such dysfunction manifests remains to be investigated. Methods We conducted a retrospective review of a cohort of 50 consecutive AHC patients for occurrence of HP related manifestations and analyzed the findings of the 6 patients, from that cohort, with such manifestations. Results Six out of 50 AHC patients manifested HP dysfunction. Three of these patients were mutation positive and 3 were mutation negative. Of the 6 patients with HP dysfunction, 3 had central precocious puberty. A fourth had short stature due to growth hormone deficiency. Two other patients had recurrent episodes of fever of unknown origin (FUO) diagnosed, after workups, as being secondary to central fever. All patients were evaluated and co-managed by pediatric neurology and endocrinology or rheumatology. Conclusion AHC was associated with HP dysfunction in about 12% of patients. Awareness of such dysfunction is important for anticipatory guidance and management particularly in the case of FUO which often presents a diagnostic dilemma. Our findings are also consistent with current understandings of the underlying pathophysiology of AHC and of the HP axis.
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characterization of severe and extreme behavioral problems in patients with Alternating Hemiplegia of childhood
Pediatric Neurology, 2020Co-Authors: Keri Wallace, Julie Uchitel, Lyndsey Prange, Joan Jasien, Melanie J Bonner, Richard Dalli, Gary Maslow, Mohamad A MikatiAbstract:Abstract Background Alternating Hemiplegia of childhood often manifests severe or extreme behavioral problems, the nature of which remains to be fully characterized. Methods We analyzed 39 consecutive patients with Alternating Hemiplegia of childhood for occurrence of behavioral problems and categorized those by severity: mild (not requiring intervention), moderate (requiring intervention but no risk), severe (minor risk to self, others, or both), and extreme (major risk). We then analyzed behavioral manifestations, concurrent morbidity, and medication responses in patients with severe or extreme symptoms. Results Two patients had mild behavioral problems, five moderate, 10 severe, six extreme, and 16 none. Extreme cases exhibited disruptive behaviors escalating to assaults. Triggers, when present, included peer-provocation, low frustration tolerance, limits set by others, and sleep disruption. Reversible psychotic symptoms occurred in two patients: in one triggered by infection and trihexyphenidyl, and in another triggered by sertraline. Of the 16 patients with severe or extreme symptoms, 13 had concurrent neuropsychiatric diagnoses. Occurrence of severe or extreme symptoms did not correlate with age, puberty, severity of intellectual disability, or mutation status (P > 0.05). A multidisciplinary team including mental health professionals comanaged all patients with severe or extreme symptoms with either behavioral therapy, medications, or both. When considering medications prescribed to more than four patients, medicines that demonstrated efficacy or partial efficacy in more than 50% of patients were alpha-adrenergic agonists and selective-serotonin-reuptake-inhibitors. Conclusions Patients with Alternating Hemiplegia of childhood (41%) often experience severe or extreme behavioral problems and, rarely, medication-triggered psychotic symptoms. These observations are consistent with current understanding of underlying Alternating Hemiplegia of childhood brain pathophysiology. Increasing awareness of these behavioral problems facilitates Alternating Hemiplegia of childhood management and anticipatory guidance.
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Alternating Hemiplegia of childhood gastrointestinal manifestations and correlation with neurological impairments
Orphanet Journal of Rare Diseases, 2020Co-Authors: Milton Pratt, Julie Uchitel, Lyndsey Prange, Melissa Mclean, Kelly J Gordon, Nancy Mcgreal, Richard J Noel, Blaire Rikard, Mary Boruta, Mohamad A MikatiAbstract:Alternating Hemiplegia of Childhood (AHC) is caused by mutations of the ATP1A3 gene which is expressed in brain areas that include structures controling autonomic, gastrointestinal, gut motility and GABAergic functions. We aimed to investigate, in a cohort of 44 consecutive AHC patients, two hypotheses: 1) AHC patients frequently manifest gastrointestinal, particularly motility, problems. 2) These problems are often severe and their severity correlates with neurological impairments. 41/44 (93%) exhibited gastrointestinal symptoms requiring medical attention. For these 41 patients, symptoms included constipation (66%), swallowing problems (63%), vomiting (63%), anorexia (46%), diarrhea (44%), nausea (37%), and abdominal pain (22%). Symptoms indicative of dysmotility occurred in 33 (80%). The most common diagnoses were oropharyngeal dysphagia (63%) and gastroesophageal reflux (63%). 16 (39%) required gastrostomy and two fundoplication. Severity of gastrointestinal symptoms correlated with non-paroxysmal neurological disability index, Gross Motor Function Classification System scores, and with the presence/absence of non-gastrointestinal autonomic dysfunction (p = 0.031, 0.043, Spearman correlations and 0.0166 Cramer’s V, respectively) but not with the paroxysmal disability index (p = 0.408). Most AHC patients have gastrointestinal problems. These are usually severe, most commonly are indicative of dysmotility, often require surgical therapies, and their severity correlates with that of non-paroxysmal CNS manifestations. Our findings should help in management-anticipatory guidance of AHC patients. Furthermore, they are consistent with current understandings of the pathophysiology of AHC and of gastrointestinal dysmotility, both of which involve autonomic and GABAergic dysfunction.
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social impairments in Alternating Hemiplegia of childhood
Developmental Medicine & Child Neurology, 2020Co-Authors: Julie Uchitel, Lyndsey Prange, Joan Jasien, Melanie J Bonner, Elie Abdelnour, April Boggs, Milton Pratt, Geraldine Dawson, Tavis Abrahamsen, Mohamad A MikatiAbstract:AIM To evaluate presence and severity of social impairments in Alternating Hemiplegia of childhood (AHC) and determine factors that are associated with social impairments. METHOD This was a retrospective analysis of 34 consecutive patients with AHC (19 females, 15 males; mean age: 9y 7mo, SD 8y 2mo, range 2y 7mo-40y), evaluated with the Social Responsiveness Scale, Second Edition (SRS-2). RESULTS SRS-2 scores, indicating level of social impairment, were higher than population means (75, SD 14 vs 50, SD 10, p 76), four moderate (66-76). All subscale domains, including social cognition, social communication, social awareness, social motivation, restricted interests, and repetitive behavior, had abnormal scores compared to population means (p<0.001). High SRS-2 scores were associated with the presence of autism spectrum disorder (ASD) and epilepsy (p=0.01, p=0.04), but not with other scales of AHC disease symptomatology. All nine patients who received formal evaluations for ASD, because they had high SRS-2 scores, were diagnosed with ASD. INTERPRETATION Most patients with AHC have impaired social skills involving multiple domains. ASD is not uncommon. High SRS-2 scores in patients with AHC support referral to ASD evaluation. Our findings are consistent with current understandings of the pathophysiology of AHC and ASD, both thought to involve GABAergic dysfunction. WHAT THIS PAPER ADDS Most patients with Alternating Hemiplegia of childhood (AHC) have impaired social skills involving multiple domains. These impairments are significant compared to population means. Most patients with AHC have high Social Responsiveness Scale, Second Edition (SRS-2) scores. Patients with AHC with high SRS-2 scores are likely to have autism spectrum disorder.
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epileptic encephalopathy with features of rapid onset dystonia parkinsonism and Alternating Hemiplegia of childhood a novel combination phenotype associated with atp1a3 mutation
Epileptic Disorders, 2020Co-Authors: Linh Tran, Joan Jasien, Jason Richards, Marie Mcdonald, Allyn Mcconkierosell, Nicholas Stong, Vandana Shashi, Mohamad A MikatiAbstract:Mutations in ATP1A3 have been found to cause rapid-onset dystonia Parkinsonism, Alternating Hemiplegia of childhood, epileptic encephalopathy and other syndromes. We report a four-year, nine-month-old boy with episodes of frequent and recurrent status epilepticus, who first began having generalized tonic-clonic seizures at four months of age. Development was normal until the age of four months, and markedly slowed down after the onset of seizures. Between the age of seven months and two and a half years, the patient had recurrent attacks of unilateral and bilateral Hemiplegia. At the age of 21 months, after a febrile illness with status epilepticus, he regressed and developed continuous severe dystonia and bradykinesia with superimposed intermittent painful dystonic spasms. Extensive neurological and genetic workup revealed a de novo p.V589F ATP1A3 mutation (NM_152296.5:c.1765G>T, NC_000019.9:g.42482344C>A). This is a novel mutation associated with a novel phenotype that shares features with epileptic encephalopathy, Alternating Hemiplegia of childhood, and rapid-onset dystonia Parkinsonism.
Frederick Andermann - One of the best experts on this subject based on the ideXlab platform.
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Infantile hypotonia and paroxysmal dystonia: a variant of Alternating Hemiplegia of childhood?
Movement disorders : official journal of the Movement Disorder Society, 2004Co-Authors: Frederick Andermann, Eva Andermann, Shunsuke Ohtahara, Peter Camfield, Katsuhiro KobayashiAbstract:We report 2 children with early onset of hypotonia and frequent episodes of paroxysmal dystonia. The episodes were abolished even by brief naps. One of the children developed Alternating Hemiplegia in the second decade. These children seem to have a variant of the now well-recognized syndrome of Alternating Hemiplegia of childhood. In that disorder, episodes of Alternating Hemiplegia develop before the age of 18 months. This syndrome must be considered in the differential diagnosis of paroxysmal dystonia in childhood.
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benign nocturnal Alternating Hemiplegia of childhood six patients and long term follow up
Neurourology and Urodynamics, 2001Co-Authors: V Chavesvischer, Fabienne Picard, Eva Andermann, Dalla B Bernardina, Frederick AndermannAbstract:Benign familial nocturnal Alternating Hemiplegia of childhood refers to recurrent attacks of Hemiplegia arising from sleep, described in young children without neurologic or mental impairment. It is probably migraine related. The authors report two unrelated patients with nocturnal attacks starting at 22 and 31 months, followed by daytime episodes in one. The authors confirm the benign course of this disorder. It is distinct from the classic malignant form of Alternating Hemiplegia of childhood.
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evidence for mitochondrial dysfunction in patients with Alternating Hemiplegia of childhood
Annals of Neurology, 1993Co-Authors: Douglas L Arnold, Kenneth Silver, Frederick AndermannAbstract:Phosphorus magnetic resonance spectra of resting muscle were obtained from 4 patients with Alternating Hemiplegia of childhood. All patients had abnormally high resonance intensities from inorganic phosphate and an abnormally law calculared cytosolic phosphorylation potential. Tow of the 4 patients had abnormally law resonance intensities from phosphocreatine and an abnormally high calculated cytosolic free adenosine diphosphare conecntration. These abnormalities are indicative of mitochondrial dysfunction. The combination of a central nervous system disorder and evidence of mitochondrial dysfunction in muscle suggests that Alternating Hemiplegia of childhood may represent a previously unrecognized phenotype of mitochondrial disease.
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Alternating Hemiplegia of childhood a study of 10 patients and results of flunarizine treatment
Neurology, 1993Co-Authors: Kenneth Silver, Frederick AndermannAbstract:Alternating Hemiplegia of childhood is a rare syndrome characterized by onset before 18 months of age of frequent attacks of Alternating paralysis, transient ocular palsies, nystagmus, choreoathetosis, and autonomic dysfunction. We describe features of 10 patients followed for up to 27 years. The mechanism of Alternating Hemiplegia remains unknown but an association to migraine is suspected because of the strong family history of migraine and aura symptoms in some patients. We treated nine patients with flunarizine, a calcium channel blocker, for up to 5 years; they showed a reduction in duration of the hemiplegic attacks, but the episodes ceased completely in only one patient. With long-term follow-up, the persistent motor, movement, and cognitive deficits are more apparent. It is not certain if the flunarizine alters this course.
Kenneth Silver - One of the best experts on this subject based on the ideXlab platform.
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benign nocturnal Alternating Hemiplegia of childhood a clinical and nomenclatural reappraisal
European Journal of Paediatric Neurology, 2018Co-Authors: Roderick P P W M Maas, Kenneth Silver, Joost Nicolai, Erikjan Kamsteeg, Salvatore Mangano, Maria Vazquez Lopez, Emilio Fernandezalvarez, Michel A A P WillemsenAbstract:Abstract Objective To describe the clinical spectrum of benign nocturnal Alternating Hemiplegia of childhood (BNAHC) including long-term follow-up data of previously published cases and to propose an underlying genetic cause of this disorder. Methods We studied the medical data of two novel patients, reviewed the literature on BNAHC, and gathered information of the most recent follow-up of published cases regarding the course of episodes, further development, attempted drugs, ancillary investigations, and sequelae. Results All patients, i.e. two novel cases and twelve patients identified in the literature (13 boys, 1 girl, age at onset four months to three years), experienced episodes of Hemiplegia during nocturnal or daytime sleep heralded by inconsolable crying. Possible triggers included stress and sleep deprivation. Eleven of fourteen patients had a family history of migraine or ‘intermittent headache’ and two sets of siblings are reported. In one case, exome sequencing revealed a heterozygous 16p11.2 deletion involving 33 genes, including the PRRT2 gene. EEG showed ictal and/or interictal contralateral slowing in four patients. Treatment efficacy was generally disappointing. A complete disappearance of attacks appeared in nearly all cases at most recent follow-up. In a remarkably high number of cases (10/14, 71%), hyperactive behaviour was reported during follow-up. Conclusion We underscore the phenotypic homogeneity including the self-limiting course of BNAHC episodes and suggest the condition be renamed ‘benign childhood Hemiplegia during sleep’ (BCHS). We propose a role for the PRRT2 gene and the resulting neuronal hyperexcitability as one of its possible underpinning mechanisms and discuss the clinical similarities of BCHS with the recognized PRRT2-related disorders.
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single center phase i ii trial of sodium oxybate in patients with Alternating Hemiplegia of childhood p04 173
Neurology, 2012Co-Authors: Aga J Lewelt, Kenneth Silver, Matthew T Sweney, Sandra P Reyna, Brian M Katchan, Mortimer Mamelak, Kathryn J. SwobodaAbstract:Objective: To investigate the safety, tolerability, dosage, and effect of sodium oxybate on ictal episodes in children with Alternating Hemiplegia of childhood (AHC). Background AHC is a sporadic neurodevelopmental syndrome of uncertain etiology, defined by paroxysmal episodes of complex abnormal movements. The clinical outcome is poor, with recurrent episodes, motor and cognitive disability, and unmanageable behavior. There is no effective pharmacologic treatment. Sodium oxybate (SO) is approved for narcolepsy to induce slow wave non-REM sleep. Hyperpolarization of neuronal cell membranes is a characteristic feature of both NREM slow wave sleep and SO-induced sleep. Theoretically, SO might be effective in aborting AHC episodes. Design/Methods: The study is an open-label, Phase I/II trial designed to obtain safety parameters and to explore potential benefit of SO. Inclusion criteria: confirmed AHC, age 0.5-25 years, >3 episodes/week, and completion of a daily AHC online event log for 6 weeks. Results: A safe and effective SO dose was identified for all 6 children who participated in a dose-escalation and safety-monitoring inpatient phase, range 40-80mg/kg/day divided qd-bid prn. Data on home SO use and its effects on episodes was collected via daily online event logs. The total episode duration, the primary outcome at 6 weeks, improved in 4 participants and worsened in 2. Adverse events included difficulty breathing, desaturations, worsening behaviors, and excessive sleepiness. The complexity of presentation and outcomes of these participants is instructive and will be reviewed. Conclusions: Impact of treatment with SO in children with AHC was difficult to interpret. Administration of SO on an as-needed basis to abort AHC episodes proved ineffective or poorly tolerated in most with prolonged use. However, 2 children remain on medication due to long-term benefits of decreased AHC episode duration and severity. Supported by: Alternating Hemiplegia of Childhood Foundation; Award Number UL1RR025763 and UL1RR025764 from the National Center for Research Resources. Disclosure: Dr. Lewelt has nothing to disclose. Dr. Sweney has nothing to disclose. Dr. Reyna has nothing to disclose. Dr. Silver has nothing to disclose. Dr. Katchan has nothing to disclose. Dr. Mamelak has nothing to disclose. Dr. Swoboda has received research support from BioMarin Pharmaceuticals and Orphamed,
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Alternating Hemiplegia of childhood early characteristics and evolution of a neurodevelopmental syndrome
Pediatrics, 2009Co-Authors: Matthew T Sweney, Jean Michel Pedespan, Kenneth Silver, Marion Gerardblanluet, Francis Renault, Alexis Arzimanoglou, Mylynda Schlesingermassart, Aga J Lewelt, Sandra P Reyna, Kathryn J. SwobodaAbstract:OBJECTIVES. Alternating Hemiplegia of childhood is a predominantly sporadic neurodevelopmental syndrome of uncertain etiology. In more than 3 decades since its description, little progress has been made in understanding its etiology or in identifying effective treatments. In 1998, in collaboration with the Alternating Hemiplegia of Childhood Foundation, an international registry was established to help document clinical outcomes and promote research efforts. PATIENTS AND METHODS. We present phenotypic data on 103 patients who met existing diagnostic criteria for Alternating Hemiplegia of childhood. Although some of these subjects may have been included in previously published reviews, our focus was directed toward the earliest manifestations of symptoms and evolution of features over time. Data sources included written questionnaires, face-to-face and telephone interviews, clinical examination, and medical charts. Characteristics of disease onset, medical comorbidities, episode triggers, diagnostic workup, and treatment are presented. RESULTS. Paroxysmal eye movements were the most frequent early symptom, manifesting in the first 3 months of life in 83% of patients. Hemiplegic episodes appeared by 6 months of age in 56% of infants. Background slowing shown by electroencephalography during typical paroxysmal events, including hemiplegic, tonic, or dystonic episodes was frequent (21 of 42 cases). Distinct convulsive episodes with altered consciousness believed to be epileptic in nature were reported in 41% of patients. Ataxia (96%) and cognitive impairment (100%) were frequent nonepisodic symptoms. Empiric pharmacologic treatment approaches offered little benefit in most subjects and resulted in adverse effects in 20% of patients. Prolonged episodes were completely or temporarily aborted during sleep in all subjects. CONCLUSIONS. This descriptive analysis of a large cohort of children indicates that paroxysmal ocular movements are an early, highly suggestive symptom, followed by paroxysmal episodes of focal dystonia or flaccid, Alternating Hemiplegia in early infancy in the majority of subjects. Current challenges in diagnosis and management contribute to poor outcomes. Early diagnosis and multicenter collaboration are needed to facilitate trials to identify more effective therapies.
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Alternating Hemiplegia of childhood or familial hemiplegic migraine?: A novel ATP1A2 mutation
Annals of neurology, 2004Co-Authors: Kathryn J. Swoboda, Emmanuel Kanavakis, Athina Xaidara, Justine E. Johnson, Mark Leppert, Mylynda Schlesinger-massart, Louis J. Ptáček, Kenneth Silver, Sotiris YouroukosAbstract:Alternating Hemiplegia of childhood (AHC) is typically distinguished from familial hemiplegic migraine (FHM) by infantile onset of the characteristic symptoms and high prevalence of associated neurological deficits that become increasingly obvious with age. Expansion of the clinical spectrum in FHM recently has begun to blur the distinction between these disorders. We report a novel ATP1A2 mutation in a kindred with features that bridge the phenotypic spectrum between AHC and FHM syndromes, supporting a possible common pathogenesis in a subset of such cases. Mutation analysis in classic sporadic AHC patients and in an additional five kindreds in which linkage to the ATP1A2 locus could not be excluded failed to identify additional mutations.
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benign familial nocturnal Alternating Hemiplegia of childhood
Neurology, 1994Co-Authors: Eva Andermann, Kenneth Silver, F Andermann, Simon Levin, Douglas L ArnoldAbstract:In infancy, two brothers developed recurrent attacks of Alternating or bilateral Hemiplegia arising exclusively out of sleep. The episodes were terminated by even brief sleep. Neither child had hypotonia, dystonic attacks, paroxysmal eye movement abnormalities, or other features characteristic of the now-classic form of Alternating Hemiplegia of childhood (AHC). The development of the brothers has so far remained normal. Both parents have a history of migraine. In the older boy, magnetic resonance spectroscopy (MRS) of muscle showed increased inorganic phosphate similar to what is found in children with AHC. In the younger brother and parents, MRS of muscle was normal. Other investigations were unrevealing. Flunarizine greatly reduced the duration of attacks. This genetically determined disorder represents a specific entity that is probably migraine-related and is easily misdiagnosed as AHC. Because of its benign course, particularly as far as mental development is concerned, it must be distinguished from classic AHC, which has a terrible prognosis.
Arn M. J. M. Van Den Maagdenberg - One of the best experts on this subject based on the ideXlab platform.
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a novel slc2a1 mutation linking hemiplegic migraine with Alternating Hemiplegia of childhood
Cephalalgia, 2015Co-Authors: Claudia M Weller, Joost Haan, Boukje De Vries, Brian G R Neville, Wilhelmina G Leen, John S Duncan, Marije A Geilenkirchen, Erikjan Kamsteeg, Michel D Ferrari, Arn M. J. M. Van Den MaagdenbergAbstract:BackgroundHemiplegic migraine (HM) and Alternating Hemiplegia of childhood (AHC) are rare episodic neurological brain disorders with partial clinical and genetic overlap. Recently, ATP1A3 mutations were shown to account for the majority of AHC patients. In addition, a mutation in the SLC2A1 gene was reported in a patient with atypical AHC. We therefore investigated whether mutations in these genes may also be involved in HM. Furthermore, we studied the role of SLC2A1 mutations in a small set of AHC patients without ATP1A3 mutations.MethodsWe screened 42 HM patients (21 familial and 21 sporadic patients) for ATP1A3 and SLC2A1 mutations. In addition, four typical AHC patients and one atypical patient with overlapping symptoms of both disorders were screened for SLC2A1 mutations.ResultsA pathogenic de novo SLC2A1 mutation (p.Gly18Arg) was found in the atypical patient with overlapping symptoms of AHC and hemiplegic migraine. No mutations were found in the HM and the other AHC patients.ConclusionScreening for...
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cacna1a mutation linking hemiplegic migraine and Alternating Hemiplegia of childhood
Cephalalgia, 2008Co-Authors: B B A De Vries, Arn M. J. M. Van Den Maagdenberg, R. R. Frants, K. R. J. Vanmolkot, L. A. E. M. Laan, A H Stam, Friederike Beker, I B Ginjaar, H Lauffer, Joost HaanAbstract:Familial hemiplegic migraine (FHM) and Alternating Hemiplegia of childhood (AHC) are severe neurological disorders that share clinical features. Therefore, FHM genes are candidates for AHC. We performed mutation analysis in the CACNA1A gene in a monozygotic twin pair with clinical features overlapping with both AHC and FHM and identified a novel de novo CACNA1A mutation. We provide the first evidence that a CACNA1A mutation can cause atypical AHC, indicating an overlap of molecular mechanisms causing AHC and FHM. These results also suggest that CACNA1A mutation scanning is indicated in patients with a severe neurological phenotype that includes paroxysmal (Alternating) Hemiplegia.
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Alternating Hemiplegia of childhood no mutations in the glutamate transporter eaat1
Neuropediatrics, 2006Co-Authors: B B A De Vries, Joost Haan, R. R. Frants, K. R. J. Vanmolkot, D. S. Gill, H. Stroink, L. A. E. M. Laan, A H Stam, Juan M Pascual, Arn M. J. M. Van Den MaagdenbergAbstract:Alternating Hemiplegia of childhood (AHC) is a severe brain disorder, mainly characterised by episodes of Hemiplegia, progressive mental retardation, and other severe paroxysmal and permanent neurological symptoms. Clinically and genetically, there is some overlap with sporadic (SHM) and familial (FHM) hemiplegic migraine, a severe monogenic subtype of migraine. Although no mutations were detected in the FHM1 CACNA1A and FHM2 ATP1A2 genes in sporadic AHC patients, a mutation was found in the FHM2 ATP1A2 gene in a family with AHC. Recently, a missense mutation was found in the SLC1A3 gene that encodes the glutamate transporter EAAT1, in a patient with Alternating Hemiplegia, episodic ataxia, seizures, and headache. Because of the remarkable clinical similarities and the potential role of glutamate in AHC, we analysed six sporadic patients with AHC for mutations in the SLC1A3 gene. No mutations were found. The SLC1A3 EAAT1 glutamate transporter gene does not seem to be involved in the pathogenesis of AHC.
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Alternating Hemiplegia of childhood: no mutations in the second familial hemiplegic migraine gene ATP1A2.
Neuropediatrics, 2004Co-Authors: Ee Kors, Joost Haan, Arn M. J. M. Van Den Maagdenberg, K. R. J. Vanmolkot, D. S. Gill, J Pascual, S. Kheradmand Kia, H. Stroink, L. A. E. M. Laan, R. R. FrantsAbstract:Alternating Hemiplegia of childhood (AHC) is a rare disorder mainly characterised by attacks of Hemiplegia and mental retardation. AHC has often been associated with migraine. Previously, we have excluded the involvement of the familial hemiplegic migraine (FHM) CACNA1A gene in four patients with AHC. A second gene for FHM was discovered recently: the ATP1A2 gene on chromosome 1q23, coding for the alpha 2 subunit of Na + ,K + -ATPase. We performed a mutation analysis of the ATP1A2 gene in six patients, using direct sequencing, but found no mutations in any of the 23 exons. Other cerebral ion channel genes remain candidate genes for AHC.
Joost Haan - One of the best experts on this subject based on the ideXlab platform.
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a novel slc2a1 mutation linking hemiplegic migraine with Alternating Hemiplegia of childhood
Cephalalgia, 2015Co-Authors: Claudia M Weller, Joost Haan, Boukje De Vries, Brian G R Neville, Wilhelmina G Leen, John S Duncan, Marije A Geilenkirchen, Erikjan Kamsteeg, Michel D Ferrari, Arn M. J. M. Van Den MaagdenbergAbstract:BackgroundHemiplegic migraine (HM) and Alternating Hemiplegia of childhood (AHC) are rare episodic neurological brain disorders with partial clinical and genetic overlap. Recently, ATP1A3 mutations were shown to account for the majority of AHC patients. In addition, a mutation in the SLC2A1 gene was reported in a patient with atypical AHC. We therefore investigated whether mutations in these genes may also be involved in HM. Furthermore, we studied the role of SLC2A1 mutations in a small set of AHC patients without ATP1A3 mutations.MethodsWe screened 42 HM patients (21 familial and 21 sporadic patients) for ATP1A3 and SLC2A1 mutations. In addition, four typical AHC patients and one atypical patient with overlapping symptoms of both disorders were screened for SLC2A1 mutations.ResultsA pathogenic de novo SLC2A1 mutation (p.Gly18Arg) was found in the atypical patient with overlapping symptoms of AHC and hemiplegic migraine. No mutations were found in the HM and the other AHC patients.ConclusionScreening for...
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cacna1a mutation linking hemiplegic migraine and Alternating Hemiplegia of childhood
Cephalalgia, 2008Co-Authors: B B A De Vries, Arn M. J. M. Van Den Maagdenberg, R. R. Frants, K. R. J. Vanmolkot, L. A. E. M. Laan, A H Stam, Friederike Beker, I B Ginjaar, H Lauffer, Joost HaanAbstract:Familial hemiplegic migraine (FHM) and Alternating Hemiplegia of childhood (AHC) are severe neurological disorders that share clinical features. Therefore, FHM genes are candidates for AHC. We performed mutation analysis in the CACNA1A gene in a monozygotic twin pair with clinical features overlapping with both AHC and FHM and identified a novel de novo CACNA1A mutation. We provide the first evidence that a CACNA1A mutation can cause atypical AHC, indicating an overlap of molecular mechanisms causing AHC and FHM. These results also suggest that CACNA1A mutation scanning is indicated in patients with a severe neurological phenotype that includes paroxysmal (Alternating) Hemiplegia.
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Alternating Hemiplegia of childhood no mutations in the glutamate transporter eaat1
Neuropediatrics, 2006Co-Authors: B B A De Vries, Joost Haan, R. R. Frants, K. R. J. Vanmolkot, D. S. Gill, H. Stroink, L. A. E. M. Laan, A H Stam, Juan M Pascual, Arn M. J. M. Van Den MaagdenbergAbstract:Alternating Hemiplegia of childhood (AHC) is a severe brain disorder, mainly characterised by episodes of Hemiplegia, progressive mental retardation, and other severe paroxysmal and permanent neurological symptoms. Clinically and genetically, there is some overlap with sporadic (SHM) and familial (FHM) hemiplegic migraine, a severe monogenic subtype of migraine. Although no mutations were detected in the FHM1 CACNA1A and FHM2 ATP1A2 genes in sporadic AHC patients, a mutation was found in the FHM2 ATP1A2 gene in a family with AHC. Recently, a missense mutation was found in the SLC1A3 gene that encodes the glutamate transporter EAAT1, in a patient with Alternating Hemiplegia, episodic ataxia, seizures, and headache. Because of the remarkable clinical similarities and the potential role of glutamate in AHC, we analysed six sporadic patients with AHC for mutations in the SLC1A3 gene. No mutations were found. The SLC1A3 EAAT1 glutamate transporter gene does not seem to be involved in the pathogenesis of AHC.
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Alternating Hemiplegia of childhood: no mutations in the second familial hemiplegic migraine gene ATP1A2.
Neuropediatrics, 2004Co-Authors: Ee Kors, Joost Haan, Arn M. J. M. Van Den Maagdenberg, K. R. J. Vanmolkot, D. S. Gill, J Pascual, S. Kheradmand Kia, H. Stroink, L. A. E. M. Laan, R. R. FrantsAbstract:Alternating Hemiplegia of childhood (AHC) is a rare disorder mainly characterised by attacks of Hemiplegia and mental retardation. AHC has often been associated with migraine. Previously, we have excluded the involvement of the familial hemiplegic migraine (FHM) CACNA1A gene in four patients with AHC. A second gene for FHM was discovered recently: the ATP1A2 gene on chromosome 1q23, coding for the alpha 2 subunit of Na + ,K + -ATPase. We performed a mutation analysis of the ATP1A2 gene in six patients, using direct sequencing, but found no mutations in any of the 23 exons. Other cerebral ion channel genes remain candidate genes for AHC.