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Clinical and Para Clinical Manifestations of Tuberous Sclerosis

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Clinical and Para Clinical Manifestations of Tuberous Sclerosis original arTiClE Clinical and Para clinical Manifestations of Tuberous Sclerosis: A Cross Sectional Study on 81 Pediatric Patients How to Cite this Article: Tonekaboni SH, Tousi P, Ebrahimi A, Ahmadabadi F, keyhanidoust Z, Zamani Gh, Rezvani M, Amirsalari S, Tavassoli A, Rounagh A, Rezayi A. Clinical and Para clinical Manifestations of Tuberous Sclerosis: A Cross Sectional Study on 81 Pediatric Patients. Iran J Child Neurol 2012; 6(3): 25-31. Seyyed Hassan TONEKABONI MD1, Abstract Parviz TOUSI MD 2, Ahmad EBRAHIMI PhD 3, Objective Farzad AHMADABADI MD 4, Tuberous sclerosis complex is an autosomal dominant neurocutaneous disease that Zarrintaj KEYHANIDOUST MD 5, presents with dermatological, neurological, cardiac, renal and ocular symptoms. Gholamreza ZAMANI MD 6, We described the variable clinical manifestations, neuroimaging findings, Age and Morteza REZVANI MD 7, sex distribution of tuberous sclerosis in a group of 81 patients referred to our clinic. Susan AMIRSALARI MD 8, Materials & Methods 9 Azita TAVASSOLI MD , Based on the diagnostic criteria, totally 81 tuberous sclerosis patients with sufficient Alireza ROUNAGH MD 10, 11 data were enrolled into the study. These children were referred by child neurologists. Alireza REZAYI MD Results 52 7 180 28 1. Associate Professor of Pediatric Neurology, The mean age of the patients was months (range, - months). There were Pediatric Neurology Research Center, Shahid girls and 53 boys. A positive familial history of TSC was seen in 29.6% of the patients. Beheshti University of Medical Sciences (SBMU), 82 7 Tehran, Iran Hypo pigmented macules were the most common manifestation ( . %). Facial 2. Professor of Dermatology, Skin Research angiofibroma, shagreen patches, café-au-lait lesions and seizure were observed in Center, Shahid Beheshti University of Medical 32 1 12 3 7 4 74 1 Sciences, Tehran, Iran . %, . %, . %. and . % of the studied cases, respectively. Infantile spasm was 3. Assistant Professor of Molecular Genetic, 32.1 % of the patients. Shiraz University of Medical Sciences, Shiraz, present in the clinical course of Iran Cortical tubers were the most common MRI finding which were seen in 21 cases 4. Fellowship of Pediatric Neurology, Assistant 25 9 4 9 Professor of Pediatrics, Pediatric Neurology ( . %). Subepandymal giant cell astrocytoma was seen in four ( . %) patients and Research Center, Shahid Beheshti University of intracranial calcification (detected by CT scan) was observed in 18 (22.2%) of the Medical Sciences (SBMU), Tehran, Iran 5. Associate Professor of Pediatric Neurology, patients. Tehran University of Medical Sciences, Tehran, Iran 6. Assistant Professor of Pediatric Neurology, Conclusion Children’s Medical Center, Tehran University of Dermatological and neurological findings were the most common symptoms in Medical Sciences (TUMS ),Tehran, Iran 7. Assistan Professor of Pediatric Neurology, tuberous sclerosis with a significant correlation between them. Thus, careful skin Qum University of Medial Sciences, Qum, Iran 8. Associate Professor, Department of Pediatric examination is necessary in epileptic patients for detection of the mentioned lesions. Neurology, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran Keywords: Tuberous sclerosis; Pediatrics; Epilepsy; Neurologic manifestations 9. Assistant Professor of Pediatric Neurology, Tehran University of Medical Sciences, Tehran, Iran Introduction 10. Assistant Professor of Pediatric Neurology, Alborz University of Medical Sciences, Karaj, Iran Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous 11. Fellowship of Pediatric Neurology, Pediatric Neurology Research Center, Shahid Beheshti disease (phacomatosis) with variable clinical manifestations (1). The incidence of University of Medical Sciences (SBMU), Tehran, the disease is approximately 1/6000- 1/10000 (2, 3). Iran Diagnosis is based on clinical and paraclinical criteria defined by the tuberous Corresponding Author: Ahmadabadi F. MD sclerosis consensus conference in 1998 .There are two groups of symptoms including Mofid Children Hospital, Tehran, Iran Tel:+98 21 22909559 major and minor criterias.The major criterias consist of:Facial angiofibromas or Email: [email protected] forehead plaques, Nontraumatic ungula or periungual fibroma, Hypopigmented macules (more than 3), Shagreen patch, Cortical tubers, Subepandymal nodules, Received: 16-May-2012 Subepandymal giant cell astrocytoma, Multiple retinal nodular hamartomas, Last Revised: 23-June-2012 Cardiac rhabdomyoma, Lymphangiomyomatosis and renal angiomyolipoma.The Accepted: 1-Jul-2012 Iran J Child Neurology Vol 6 No 3 Summer 2012 25 Clinical and Para clinical Manifestations of Tuberous Sclerosis: A Cross Sectional Study on 81 Pediatric Patients minor criterias include:Dental Pits (more than 14), Other neurological manifestations of TSC include Hamartomatous rectal polyps, Bone cysts, Cerebral whte cortical tubers (Fig 1), subepandymal nodules (Fig 2) matter radial migration lines, Nonrenal hamartomas, and subepandymal giant cell astrocytoma that may lead Retinal achromatic patch, Confetti skinlesions, Multiple to seizure attacks. Cortical tubers tend to be in the front renal cysts.When there are two major criteria or one parietal region. Ventricular dilation is seen in 55% of TS major and two minor criteria the diagnosis is established cases and cerebral tumors in 1.7-15% with a mean age as definite TSC. The term probable TS is used when of 13.5 years (11). one major and one minor criteria are detected (2). Only The skin manifestations of TSC tend to be the most one major feature or two or more minor criteria without prevalent findings (4). The hypo pigmented macules or any major feature mentions the possibility of tuberous ash leaf lesions are the most important, early onset and sclerosis (2). characteristic dermatological findings (Fig 3). These The central nervous system involvement is the most lesions are seen in 4.7% of the normal population, but common finding in tuberous sclerosis that leads to their prevalence is 97% in children with TSC (4). They are morbidity and mortality (4). These manifestations were located on the trunk and buttocks and are easily identified first described by D M Bourneville in 1880. Before with the wood lamp. Other skin lesions such as café-au- that, Von Recklinghausen had described a newborn lait macules, confetti like macules, periungual fibromas, who had died of respiratory distress and at post mortem forehead plaques and shagreen patches may also be examinations a great number of cerebral sclerosis was observed. The latter is seen soon before puberty (3). detected (3). Sometimes cardiac rhabdomyoma is the earliest Epilepsy is the most common presenting symptom in diagnostic finding in TSC. These hamartomas of the tuberous sclerosis. In 98% of these patients seizure is heart remain asymptomatic and regress in size and discovered and 75% of them have a seizure attack in the number till 6 years of age in 58-74% of the patients (4). first year of life (4). Seizure control is difficult and they Renal involvement is seen as angiomyolipomas (AML) tend to be refractory and intractable in more than 50% of or cysts in TSCs. They are the second cause of death in the cases despite pharmacological and surgical treatment these patients and the first fatal cause in patients older than (5). Even cases with a good response to antiepileptic 30 years of age. AML is the most common major renal drugs in the beginning of therapy will have frequent finding and is often bilateral. Only a fair correlation was relapses (6). found between age and renal involvement (12). Ocular Surgery is one of the treatment options of seizures, but manifestations of TSC including retinal hamartomas the outcome is best when the EEG-MRI and semiology occur in less than 50% of the patients and are bilateral of seizure indicate a surgically accessible location (6). in one third of the cases. There is no correlation between Recent reports on the direct approach to neoplastic age and ocular manifestations (2). lesions show that in cases with an increased intracranial pressure, surgical interventions may provide a better Materials & Methods outcome (7). Surgery is not indicated in the presence Eighty-one children (age range: 7 months to 15 years) of bilateral epileptogenic zones, progressive epileptic based on the diagnostic criteria and sufficient data were encephalopathy and severe mental retardation. enrolled into the study. In some cases with drug resistant epilepsy and those These children were referred by dermatologists and who are waiting for surgical intervention, the ketogenic child neurologists practicing in Tehran and other cities diet has been considered. This diet can decrease more to the neurology clinic of Mofid children hospital from than 50%of seizures in 90% of cases (8). It seems September 2009 till July 2012. Clinical and paraclinical that antiepileptic treatment before the onset of seizure information based on careful physical examination and reduces the severity of epilepsy and the risk of mental systematic review of the patients were collected by a retardation in TSC if EEG shows multifocal activity fellow in child neurology. without clinical seizure (9). This information was collected on a questionnaire and 26 Iran J Child Neurology Vol 6 No 3 Summer 2012 Clinical and Para clinical Manifestations of Tuberous Sclerosis: A Cross Sectional Study on 81 Pediatric Patients statistically analyzed by SPSS 12 package. Informed Iranian population.
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