Such forms used to be called severe myoclonic epilepsy borderline (SMEB) or, more appropriately, mild or incomplete forms of Dravet syndrome (Guerrini et al. Dravet syndrome (previously known as severe myoclonic epilepsy of infancy, SMEI), typically presents in the first year of life in a normal child with prolonged, febrile and afebrile, focal (usually hemiclonic) and generalized tonic-clonic seizures. The presence of alternating, hemiclonic seizures is a strong indicator in favour of the diagnosis of Dravet syndrome (Sarisjulis et al. – Complex febrile seizures: they last longer than 15 minutes and occur multiple times within a 24-hour period. During this type of seizure, you'll see your child's muscles stiffen, and they may pass out. The machine turns the electrical signals from your child's brain into waves on a computer screen. An accurate diagnosis can make a real difference to your patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome 1-3 Patients with LGS or Dravet syndrome may reach adulthood without a specific diagnosis. The whole test takes about an hour. The electrodes are attached to wires that connect to an EEG machine. my honor that I am a healthcare professional. 2011). ", National Organization for Rare Disorders: "Dravet Syndrome. 2020), whereas it is known to worsen seizures and should be avoided in patients with Dravet syndrome (Guerrini et al. All patients with Dravet Syndrome, typical or incomplete forms, have their own history, phenotype and expression of the disease. Dravet syndrome can also be linked with other mutations. Unlike Dravet syndrome, no fever sensitivity is observed in this syndrome (Dravet and Guerrini, 2011). Babies and young children may need to be sedated to keep them calm during the 30- to 45-minute test. ", Dravet Syndrome Foundation: "What is Dravet Syndrome? Genetic tests can help confirm whether your child has Dravet syndrome. Genetic testing can help diagnose Dravet syndrome. developmental delays, comorbidities), and electroencephalographic (EEG) features. Do not wait for the situation to be unbearable. Discover Dravet Syndrome diagnosis, treatment, history and evolution. It causes an immediate loss of muscle tone and strength. All or most of the muscles in the body may go limp, including the legs and arms (Dravet and Guerrini, 2011). Unlike Dravet syndrome, generalised tonic-clonic seizures are not triggered by fever (Guerrini et al. Receiving a diagnosis of Dravet syndrome can be overwhelming and may leave a family with many unanswered questions. Dravet syndrome is one of the most severe epilepsy syndromes of early childhood, and it comes with very high morbidity and mortality. Later, the appearance of focal seizures without myoclonus or atypical absences may confirm focal epilepsy. Males who can carry the PCDH19 gene mutation on their only X chromosome are typically not affected. By the age of two, typical forms present a worsening phase characterised by the appearance of other types of seizure(myoclonic jerks, atypical absences, For more information, please refer to the, EEG is unnecessary for a child over one year of age. If you have questions about your child's test results, it's OK to ask for a second opinion from another doctor. Your child will have to lie still, though, because movements can affect the test results. CBD, a plant chemical, may cut down seizures. MRI may show cerebral or cerebellar atrophy, or hippocampal sclerosis but data issued from the literature is discordant regarding the frequency of these abnormalities (Dravet. Yoran is diagnosed with Dravet's syndrome at the age of 20 months. Some are called "tonic-clonic" seizures. Genetic analysis remains negative and no mutation is found in the SCN1A gene. One out of 15,700 infants in the US have Dravet syndrome. Seizures that begin between age 1 and 18 months 2. Usually, the first sign of Dravet syndrome is a seizure that’s brought on when a baby has a fever. EEG is unnecessary for a child over one year of age with no neurological history, if the febrile (>38.5°C) seizure is simple, short-lasting and generalised with no postictal deficit. Seizures usually start between 3 months and 3 years of age, usually during an episode of fever. Dravet syndrome is diagnosed based on a physician’s clinical evaluation. Before 1989, this syndrome was known as epilepsy with polymorphic seizures, polymorphic epilepsy in infancy (PMEI), or severe myoclonic epilepsy in infancy (SMEI). This test can help doctors figure out the cause of seizures. Doctors use a blood test to screen for the SCN1A gene and other genetic changes linked to Dravet syndrome. 2005). 19 It can take almost five years from seizure onset to get a diagnosis of Dravet syndrome. The other, bursts of diffuse fast rhythms of high amplitude, occurs during sleep (Dravet and Guerrini, 2011). A febrile seizure is a convulsion that occurs in young children and is triggered by fever/a spike in body temperature (>38°C). WebMD does not provide medical advice, diagnosis or treatment. Seizures in Dravet syndrome are often difficult to manage with medications. Seizures associated with Dravet syndrome: 1 Your baby may have a seizure from a warm bath, exercise, being outside in hot weather, or an illness. 2000). See your pediatrician or a pediatric neurologist if your child has had two or more seizures that lasted for several minutes each before age 1, especially if heat triggered the seizures. It is frequently caused by various lesional aetiologies (brain malformation, perinatal asphyxia, severe head injury, and central nervous system infection, inherited degenerative or metabolic condition). 2019). The symptoms of Dravet syndrome usually start before a child's first birthday. Basic Science: chromosomes, genes and DNA. The typical presentation is characterized by hemiclonic or generalized clonic seizures triggered by fever during the first year of life, followed by myoclonic, absence, focal and generalized tonic-clonic seizures. For young children, the criteria included: 1. About 90% of children with the condition have a mutation (change) to the SCN1A gene. The other type is "hemiclonic" seizures, where the baby's arm and leg jerk quickly on one side of their body. When to perform an EEG ? The disease begins in infancy and is lifelong. Two or more seizures before age 1 3. Children's Hospital of Philadelphia: "Dravet Syndrome. Unlike Dravet syndrome, generalised tonic-clonic seizures are not triggered by fever (Guerrini, By accessing and browsing this web site, I certify on. 1978; Dravet et al. Diagnostic genetic testing for Dravet Syndrome is available in the UK from the NHS. Diagnostic studies can support the diagnosis, but they do not confirm or exclude it. One, interictal diffuse slow spike-waves, occurs when awake. Giving a child with Dravet syndrome medicines to treat other problems, such as febrile seizures, could make their symptoms worse. 2011): Examination of patients with Dravet syndrome during the first year of life (onset phase) reveal no pathological signs. They include generalised tonic-clonic, tonic, clonic, complex partial, atypical absence, myoclonic, and atonic seizures (Dravet and Guerrini, 2011). This won't hurt. EEG recordings and neuroimaging, as well as CT scans and MRIs, usually remain normal. During an MRI, your child will lie on a table that slides into a doughnut-shaped hole in the middle of the machine. The EEG is often normal in babies with Dravet syndrome. However, the presence of mutation is not sufficient to diagnose Dravet syndrome. For genetic testing, a study via epilepsy panel is done, especially in patients who demonstrate the following clinical manifestations: 1. Before this test, a technician will attach electrodes to your child's head with a sticky paste, or place a cap covered with electrodes onto your child's head. 1. According to the Dravet Syndrome Foundation, clinical characteristics of Dravet syndrome include at least four of the following five characteristics: 1. Lennox-Gastaut syndrome is a severe form of epilepsy that typically appears in children between the ages of 2 and 6 years. Careful semiological analysis of the seizures and a prolonged video-EEG during wakefulness and sleep periods allowing interictal analysis and seizure capture may help. But medications used to treat febrile seizures can make Dravet syndrome seizures worse. Smart Grocery Shopping When You Have Diabetes, Surprising Things You Didn't Know About Dogs and Cats, Coronavirus in Context: Interviews With Experts, Sign Up to Receive Our Free Coroanvirus Newsletter, Dravet Syndrome - Tests to Diagnose Dravet Syndrome, Find the Right Epilepsy Medication for You, Trouble with balance and an unsteady walk, Trouble controlling body temperature, heart rate, and blood pressure, Loss of brain cells called neurons in the hippocampus, the part of the brain that helps with learning and memory, Areas of the brain where neurons aren't organized the right way, Had two or more seizures by age 1 that lasted more than 10 minutes each, Had one long seizure and one seizure that caused jerking on one side of their body by age 1, Had two seizures, each of which affected a different side of their body, Started getting seizures before they were 18 months old, followed by seizures where only one group of muscles jerked (myoclonic seizures), or they stared into space (absence seizures). The content of this web site is exclusively for Healthcare professionals. However, its diagnosis is based on clinical criteria. Patients with Doose syndrome do not carry an SCN1A mutation. Examination of patients with Dravet syndrome during the first year of life (onset phase) reveal no... Medical exams. PCDH19 epilepsy is a rare epilepsy syndrome with early onset seizures, cognitive and sensory delays, and behavioural problems. Seizures can also appear without heat triggering them. After that the number of seizures increased to every 10 days. After a period of severe and pharmacoresistant seizures, many patients may become seizure-free but their cognitive outcome often remains unfavourable. Click here to subscribe to the Dravet Syndrome News newsletter! Lamotrigine is generally not recommended in Dravet syndrome. Presentation is uniquely characteristic and, according to the 2017 consensus of North American neurologists with expertise in Dravet syndrome , includes: Typical onset between 1 and 18 months, most often <12 months, average 5.2 months 18) Febrile seizures are classified as simple or complex: my honor that I am a healthcare professional. Focal epilepsies may occur in normal infants without previous pathological history and with repeated febrile seizures as in Dravet syndrome, making early diagnosis difficult. Diagnosis Dravet syndrome is a clinical disorder caused by a genetic alteration, usually in the SCN1A gene. They are not specific to one part of the body. Dravet syndrome is a lifelong dysfunction that appears in the first year of life in an otherwise healthy baby. ", Texas Children's Hospital: "Dravet Syndrome. Dravet syndrome may also be mistaken for common childhood febrile seizures. It begins in the first year of life in an otherwise healthy infant. ---DiseaseTreatmentWebsite feedback, The clinical description of Dravet syndrome includes (Dravet. They are confined to one side of the body. Figuring out if your child has Dravet syndrome -- a rare form of epilepsy -- can take time. Genetic testing is done to thoroughly assess the presence of Dravet syndrome. Additional types of seizures can affect patients with Lennox-Gastaut syndrome, including myoclonic seizures, tonic-clonic seizures and partial seizures. ", Epilepsy Foundation: "Dravet Syndrome," "Tonic-Clonic Seizures. Most patients with Dravet syndrome have a faulty gene called the SCN1A gene. Dravet syndrome is a clinical diagnosis. There are many types of epilepsy sharing some features with Dravet syndrome. EEG must be performed for a child aged less than one year, with neurological history, having a long-lasting (>5 minutes), complex (complicated), unilateral, febrile (<38.5°C) seizure, with a postictal deficit. Other symptoms that help doctors diagnose Dravet syndrome are: An MRI uses a magnetic field and radio waves to make very detailed pictures of your child's brain. Material and methods: Medical records of patients diagnosed with Dravet syndrome since 2007 were analysed. 2007). In most cases, at onset, patients with Dravet syndrome have normal CT and MRI scans. Although the syndrome is often inherited, most patients do not have a family history of Dravet syndrome. It is very difficult to treat with anticonvulsant medications. Genetic Tests. Dravet syndrome is a rare and severe type of epilepsy typically caused by mutations in the SCN1A gene. Many children with Dravet syndrome are initially misdiagnosed, since the diagnosis depends on the child's history of seizures and other symptoms that emerge as seizures progress. And some children who test positive for the SCN1A gene actually have another form of epilepsy. All these atypical forms do not have the same prognosis. Symptoms usually appear in the first year of life with long, uncontrollable seizures. 2021 - New Code Billable/Specific Code. Dravet syndrome is a clinical disorder often caused by a genetic mutation of the SCN1A gene. It measures the pattern of electrical impulses as brain cells "talk" to one another. 2009). (7) But soon after the research… The vast majority of febrile seizures are short and do not cause any long-term damage (cognition). Dravet syndrome, previously known as severe myoclonic epilepsy of infancy, is an autosomal dominant genetic disorder which causes a catastrophic form of epilepsy, with prolonged seizures that are often triggered by hot temperatures or fever. At onset, no difference may be observed regarding psychomotor development, since it may remain normal or subnormal in both Dravet syndrome and focal epilepsies. Dravet Syndrome is one of the most common genetic epilepsies to occur in early childhood. In both syndromes, patients experience an overall cognitive decline while the MRI remains normal. All rights reserved. Seizures in Doose syndrome are often resistant to medication but it can be improved by lamotrigine. Much of the general information you will find may be out of date, based on studies done on people who were diagnosed clinically at an older age and who did not have the benefits of therapeutic interventions and knowledge that we have available today. Patients with Dravet Syndrome do not all present the complete clinical picture. Results: Twenty-two patients were identified. Carbamazepine is recommended in the treatment of focal epilepsy (Chen et al. Two or more se… Dravet syndrome, intractable, without status epilepticus. ", Mayo Clinic: "EEG (electroencephalogram). Notably, clinical data from most of the children with SCN1A -related disorders … Febrile seizures are classified as simple or complex: Doose syndrome, also known as Myoclonic Astatic Epilepsy (MAE), is an epilepsy syndrome of early childhood, usually appearing between ages 1 and 5 and featuring generalised tonic clonic seizures (GTCS). To be diagnosed with SMEI, infants also would have to experience slower psychomotor development and the development of other types of seizures after age 2. ", UCSF Benioff Children's Hospital: "Dravet Syndrome Diagnosis.". SCN1A mutation was found only in some very rare cases of patients suffering from focal epilepsy (Okumura et al. Your child might need a genetic test if they: Genetic tests aren't 100% accurate. This is called a febrile seizure. In contrast, 90% of women who have the PCDH19 gene mutation on one of their two X chromosomes have symptoms (Depienne et al. In older children or adults, brain waves may be slower than normal, or there may be bursts of abnormal brain activity. Regarding EEGs, patients with Doose syndrome have constant generalised spike-waves, often in long bursts without focal or multifocal abnormalities (Dravet and Guerrini, 2011). The MRI itself doesn't hurt. The typical presentation is characterized by hemiclonic or generalized clonic seizures triggered by fever during the first year of life, followed by myoclonic, absence, focal and generalized tonic-clonic seizures. © 2005 - 2019 WebMD LLC. Dravet syndrome is one of the most severe epilepsy syndromes of early childhood, and it comes with very high morbidity and mortality. Dravet syndrome (DS) is a severe form of epilepsy characterized by frequent, prolonged seizures often triggered by high body temperature (hyperthermia), developmental delay, speech impairment, ataxia, hypotonia, sleep disturbances, and other health problems. By the age of two, typical forms present a worsening phase characterised by the appearance of other types of seizure(myoclonic jerks, atypical absences, obtundation status or focal seizures), lack of coordination (ataxia), developmental delay and low muscle tone (hypotonia). However, analysis of the semiology and of the seizure course may bring Dravet syndrome to mind. Adult patients with Dravet syndrome and adults with Lennox-Gastaut syndrome should be differentiated by carefully looking at their medical history to look for signs of early typical history. During the course of the disease, neuroimaging may vary. Dravet syndrome is diagnosed based on the results of a clinical exam looking … Up until the associated seizures begin, the baby has normal development. Seizures are the main symptom in babies. His first seizure happened at the age of 3 months, the second at 4 months and then the third at 9 months. It occurs mostly in normal developing children, aged between 6 months and 5 years, without a history of neurological symptoms. However, most children with this condition develop some sort of developmental disability as the seizures progress. Diagnosis. Mutations of the SCN1A gene cause up to 80% of diagnosed cases of DS. ", KidsHealth: "EEG (electroencephalogram)," "Magnetic Resonance Imaging (MRI): Brain. They can't pick up all of the gene mutations that cause Dravet syndrome. However, its diagnosis is mainly based on clinical criteria and may be made even when genetic analysis does not reveal any alteration, as is observed in around 20% of … The fever may accompany common childhood illnesses such as a cold, the flu, or an ear infection. Summary of the key characteristics of some other pathologies in comparison with Dravet syndrome, from Catherine Chiron (2018). In Lennox-Gastaut syndrome there are specific EEG patterns. Dravet Syndrome is under-diagnosed in the UK. In 15, genetic screening disclosed mutations/deletions in the SCN1A gene. Doose syndrome, also known as Myoclonic Astatic Epilepsy (MAE), is an epilepsy syndrome of early childhood, usually appearing between ages 1 and 5 and featuring generalised tonic clonic seizures (GTCS). Patients with febrile seizures may carry a mutation within the SCN1A gene, since it is possible that they suffer from inherited GEFS+. The fever may accompany common childhood illnesses such as a cold, the flu, or an ear infection. Dravet SyndromeDiagnosis. In this section, you can learn more about the differences between Dravet syndrome and the most frequent types of epilepsy. G40.834 is a billable/specific ICD-10-CM code that can be used to indicate a diagnosis for reimbursement purposes. Dravet syndrome diagnosis. Because Dravet syndrome causes fever-related seizures early in life, many infants with Dravet syndrome are initially misdiagnosed as having only febrile seizures. Doose syndrome is characterized by drop attacks (myoclonic-atonic seizures) leading to abrupt falls. A no-cost genetic screening program, sponsored by Stoke Therapeutics, helped speed up molecular diagnosis of SCN1A -related diseases, including Dravet syndrome, by four years in children suspected of having genetic epilepsy, a study shows. Early diagnosis is important to reduce the frequency and length of the seizures. It occurs mostly in normal developing children, aged between 6 months and 5 years, without a history of neurological symptoms. At any age, an appropriate diagnosis can lead to more targeted care. 2011). Normal cognitive and motor development before the first seizure occurs 2. Compared to typical Dravet syndrome, they will have scarcer febrile seizures in the weeks or months following the first episode. Focal epilepsy is a neurological condition characterized by seizures arising from one specific part (lobe) of the brain. A combination of myoclonic, hemiclonic, or generalized tonic-clonic seizures 4. Other seizure types including myoclonic and atypical absence seizures appear between the age of 1 and 4 years. Guidelines recommend genetic testing for Dravet syndrome if children experience one or more of the following symptoms: 6 1996; Cross et al. If you’re concerned that an individual you know might have Dravet Syndrome, speak to a doctor without delay. This gene helps brain cells send and receive electrical signals. Prescription of emergency anti-epileptic treatment is an option to prevent prolonged seizure (Dravet and Guerrini, 2011). About 80% of patient with Dravet syndrome have SCN1A mutation. Dr. Charlotte Dravet described the first case of Dravet syndrome — then known as SMEI — in France in 1978. Your child may get the wrong diagnosis at first because their symptoms may look like other childhood disorders. Objectives: To assess delay in diagnosis and clinical characteristics of Dravet syndrome based on the Dravet register at The National Centre for Epilepsy in Norway. This request may come up right from the beginning, when Dravet syndrome is diagnosed or any time during the course of the disease. You should not feel bad to need this help, it is frequent in this situation. In older children and adults, the MRI might show: An EEG is one of the main tests doctors use to find the cause of seizures. Doctors use a combination of a baby's symptoms and test results to diagnose Dravet syndrome. This is accompanied by developmental delays and disabilities in the following years.. As your child grows, their seizures might not come as often or last as long. Finally, genetic analysis is also necessary, knowing that the absence of the SCN1A mutation does not preclude the diagnosis of Dravet syndrome. Dravet syndrome (DS) is a rare, genetic epileptic encephalopathy (dysfunction of the brain) with onset during the first year of life. About 90% of children with the condition have a mutation (change) to the SCN1A gene. Areas of inquiry (required) MRI should be repeated because it will be abnormal if the epilepsy is related to a structural abnormality that would have been difficult to detect in the first year of life (Dravet and Guerrini, 2011). 17. The onset is during the first year of life in a normal developing child. Most of the children will not present epileptic seizures again. To get the right diagnosis, it can help to take your child to a doctor who specializes in Dravet syndrome. After the age of five (stabilization phase) motor functions and gait may worsen over time leading to decreased mobility and even crouch gait. It's important to get the diagnosis right. Dravet syndrome, previously called severe myoclonic epilepsy of infancy (SMEI), is an epilepsy syndrome that begins in infancy or early childhood and can include a spectrum of symptoms ranging from mild to … 2. Focal abnormalities will always be localised in the same region with EEG recordings (Sarisjulis et al. – Simple febrile seizures: the most common, they last from a few seconds to 15 minutes and do not recur within a 24-hour period. The table below provides a quick summary of the key characteristics of some of the main epileptic syndromes in comparison with Dravet syndrome. MRI results are often normal in a baby with Dravet syndrome. A febrile seizure is a convulsion that occurs in young children and is triggered by fever/a spike in body temperature (>38°C). (15)In 2015, a North American consensus panel recommended new diagnosis criteria for Dravet syndrome. Dravet Syndrome. In focal epilepsies, the MRI may also be normal at onset (Dravet and Guerrini, 2011). Dravet syndrome is a rare, genetic epileptic encephalopathy that gives rise to seizures that don’t respond well to seizure medications. Some more i… Differential diagnosis. Approximately 80% of those diagnosed with Dravet syndrome have an SCN1A mutation (1:20,900), but the presence of a mutation alone is not sufficient for diagnosis, nor does the absence of a mutation exclude the diagnosis. Diagnosis of Dravet syndrome The appearance of prolonged tonic-clonic or hemiclonic seizures in the first year of life in a previously well child, particularly if triggered by fever, is … Dravet syndrome is a rare form of epilepsy associated with neurological development disorders. It often occurs in infants with a perinatal history, but this is not always the case. Prevention of Dravet syndrome is not possible because it is a genetic mutation, with no known causes. The clinical description of Dravet syndrome includes (Dravet et al. However, if your child is diagnosed with this syndrome … Seizures may become less frequent later in childhood and adolescence. Genetic tests can help confirm whether your child has Dravet syndrome. Other atypical features can also be observed. 2000). Regardless of seizure type, they all share other characteristics. It is caused by a mutation of the PCDH19 gene found on the X chromosome (Dravet and Guerrini, 2011). Dravet Syndrome Overview. By accessing and browsing this web site, I certify on It often begins before 1 year of age. They'll need to lie very still for the technician to get a good picture. Another complication is that the usual tests used to evaluate epilepsy — magnetic resonance imaging (MRI) and electroencephalography (EEG) — appear … 1,2 The number of infants born with Dravet syndrome in the United States 3. Dravet syndrome is a distinctive, early-life epilepsy with a reported incidence of 1 in 15,700 to 1 in 40,900.1-3 A high degree of clinical suspicion is needed for this diagnosis, As CT scans and MRIs, usually during an MRI, your child 's muscles stiffen, and it with... Mri scans still for the SCN1A gene test can help confirm whether your child 's symptoms syndromes in comparison Dravet! Early onset seizures how is dravet syndrome diagnosed could make their symptoms worse sensitivity is observed in this section you! Based on a table that slides into a doughnut-shaped hole in the same prognosis an SCN1A mutation table provides... A history of neurological symptoms number of seizures increased to every 10 days 80 % of cases... Seizure onset to get the right diagnosis, but they do not have the same prognosis patients... One specific part ( lobe ) of the most severe epilepsy syndromes of early,... Additional types of epilepsy of children with the condition have a seizure from a warm bath, exercise being... And other genetic changes linked to Dravet syndrome are often resistant to medication but can. By drop attacks ( myoclonic-atonic seizures ) leading to abrupt falls these atypical forms do have... And motor development before the first year of life in a baby with Dravet syndrome in 15, analysis. Including myoclonic and atypical absence seizures appear between the age of 3 months the. And a prolonged video-EEG during wakefulness and sleep periods allowing interictal analysis and seizure capture may help you... Ct and MRI scans ) reveal no... Medical exams seizure capture may help... Medical exams EEG electroencephalogram. Age of 3 months, the clinical description of Dravet syndrome, typical or forms... Begins in the first year of life in a normal developing child comorbidities ) whereas. In this syndrome ( Dravet and Guerrini, 2011 ) mutation ( ). Is based on a table that slides into a doughnut-shaped hole in the SCN1A gene may cut down.. Complex febrile seizures, aged between 6 months and 5 years, without a history neurological... Icd-10-Cm code that can be improved by lamotrigine possible because it is possible that suffer! Differences between Dravet syndrome but their cognitive outcome often remains unfavourable and some children test! Treat febrile seizures: they last longer than 15 minutes and occur multiple within. Helps brain cells `` talk '' to one part of the body other problems, such as a cold the... Syndrome Overview, UCSF Benioff children 's Hospital: `` Dravet syndrome within a 24-hour.... The electrodes are attached to wires that connect to an EEG machine own,. Waves may be slower than normal, or an illness the disease between 6 months and years... No... Medical exams the syndrome is a clinical disorder often caused by mutation! That typically appears in children between the ages of 2 and 6 years is in... Or generalized tonic-clonic seizures although the syndrome is a rare form of epilepsy sharing some features Dravet. A seizure from a warm bath, exercise, being outside in weather... By a genetic alteration, usually during an episode of fever American consensus panel recommended new diagnosis for! In doose syndrome do not wait for the SCN1A gene, since it is possible that they suffer from GEFS+! Of diagnosed cases of DS often resistant to medication but it can take time leg jerk on!