About 1 in 15,700 infants are born with Dravet syndrome, and up to 80 percent of them have a mutation in their SCN1A gene. (1) For the most part, the disorder is not inherited — about 85 percent of people with Dravet syndrome have a de novo (new) mutation not passed to them from their parents. (2) It’s a rare and severe form of epilepsy, and the hallmark symptoms of Dravet syndrome involve seizures — a surge of electrical activity in the brain that results in physical and mental manifestations.
Initial Symptoms of Dravet Syndrome
Infants with Dravet syndrome experience their first seizure in their first year of life, typically when they are 6 to 10 months old. This first seizure is usually febrile, or related to fevers. A study found that all but one of the children in the research had febrile seizures, which was the first symptom of the syndrome for about 75 percent of the children. (2) These febrile seizures are usually so-called tonic-clonic seizures characterized by stiffness, unconsciousness, and jerking. Tonic-clonic seizures, also known as grand mal seizures, are the type that most people associate with epilepsy. (3) In infants with Dravet syndrome, febrile convulsions may be unusually long, sometimes lasting 15 to 30 minutes or longer (such seizures are called febrile status epilepticus and can be life-threatening). Infants with Dravet syndrome should be taken to emergency care if their convulsions are this prolonged. (4) Early seizures often involve just one side of the body, but they can also affect both sides of the body and only cause repeated jerking (clonic seizures). These seizures can occur without a fever and may be triggered by slight changes in body temperature, such as from warm baths, exertion, and warm weather. (5)
Dravet Syndrome and Seizures
Dravet syndrome was once known as severe myoclonic epilepsy of infancy, or SMEI. When the syndrome was first described in the late 1970s and early 1980s, myoclonic seizures were a common feature. (6) These seizures are characterized by the repeated jerking or twitching of muscles lasting no more than a second or two. They usually cause abnormal movements on both sides of the body simultaneously. (7) Research suggests about 85 percent of children with Dravet syndrome experience myoclonic seizures between age 1 and 5. (8) People with Dravet syndrome can also experience other types of seizures, including:
Absence seizures, which cause a person to “blank out” mentally and stare off into space for less than 10 seconds (though it is not simple daydreaming)Atypical absence seizures, which are similar to absence seizures but last for more than 20 seconds and cause a change in muscle tone and movement such as lip smacking and fluttering eyelids (9)Atonic seizures, which cause a severe loss of muscle tone that makes the head or body go limp (10)Focal aware seizures, which start in one area of the brain and cause the person to be frozen but aware of surroundings for less than two minutes (11)Impaired awareness seizures, which are similar to focal aware seizures except that the person is not aware of his or her surroundings (12)Convulsive seizures, which include: tonic, in which seizures are sustained but transient, with asymmetrical posturing of the trunk or extremities, or tonic deviation of the eyes; clonic, with repetitive, rhythmic contractions of specific muscle groups of the limbs, face, or trunk; and tonic-clonic, characterized by an initial tonic phase followed by a clonic phase, usually bilateral and generalized. (3)Status epilepticus, a serious condition in which any of the above seizures last for more than five minutes, or a person doesn’t recover between multiple seizures that occur in quick succession (13)
Aside from temperature changes, the seizures may be triggered by emotional stress or excitement, infections, or flashing lights or patterns (photosensitivity seizures). (8)
Other Dravet Syndrome Symptoms and Issues
Children with Dravet syndrome usually have seemingly normal development until age 2, at which point they may lose developmental milestones. In particular, the children may have mild to severe mental retardation, delayed language and speech issues, movement and balance issues, and personality issues, such as social isolation and frequent mood swings. The degree of developmental delay corresponds to the frequency of seizures and status epilepticus. Other problems include:
Orthopedic issues, such as painful foot problems caused by low muscle toneUnsteady walkingCrouched gait (in older children and adults)Sleeping difficultiesGrowth and nutrition issuesChronic infectionsPoor regulation of body temperature and sweating due to autonomous nervous system issuesSensory processing disorders that result in sensitivity to environmental stimuli
Dravet syndrome also increases risk of death due to a condition called sudden unexpected death in epilepsy, as well as seizure-related accidents (such as drowning and infections). (1,8,14)
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. But medications used to treat febrile seizures can make Dravet syndrome seizures worse. (15) In 2015, a North American consensus panel recommended new diagnosis criteria for Dravet syndrome. For young children, the criteria included:
Seizures that begin between age 1 and 18 monthsRecurrent tonic-clonic or hemi-convulsive seizuresMyoclonic seizures that arise by age 2 years, followed by various other types of seizuresSeizures triggered by hyperthermia or other triggers, including flashing lights, bathing, and overexertionNormal results for developmental tests, neurological exams, MRIs, and EEG readings
In older children or adults who were not previously diagnosed (and whose childhood histories are unavailable), the criteria includes:
Persistent seizures, including myoclonic, convulsive, atypical absence, and tonic seizuresDecreased frequency of status epilepticusDecreased frequency of seizures triggered by hyperthermiaIntellectual disability that is evident by 18 to 60 months of ageSeizures that worsen because of sodium channel blocking medicationsNeurological abnormalities by age 3 or 4 years, such as crouched gait, coordination issues, poor dexterity, and low muscle toneMRI scans that are normal but may show mild generalized atrophy or hardening of the hippocampal brain regionEEG that shows evidence of epileptic activity (16)
Genetic Tests for Dravet Syndrome
Blood tests are not used to diagnose Dravet syndrome. But given that the majority of people with the syndrome have a SCN1A gene mutation that causes it, blood tests can sometimes confirm diagnosis. (8) One study suggested that family members should consider genetic testing for Dravet syndrome if their loved ones experience any of the following:
At least two prolonged seizures by age 1A prolonged seizure plus a hemi-clonic seizure, which causes a sustained, rhythmic jerking of one side of the body, by age 1Two seizures that affect alternating sides of the bodyA history of seizures before age 18 months and a later emergence of myoclonic or absence seizures (17)
Other Dravet Syndrome Causes
Having an SCN1A mutation does not necessarily mean that a person has Dravet syndrome. The mutation can cause other seizure disorders, such as febrile seizures, febrile seizures plus, generalized epilepsy with febrile seizures plus, and intractable childhood epilepsy with generalized tonic-clonic seizures. (5.) Likewise, other genetic mutations can cause Dravet syndrome or a Dravet-like syndrome. For example, a mutation in the PCDH19 gene can cause a clinically overlapping syndrome that is sometimes mistaken for Dravet syndrome. Other genetic mutations that cause Dravet syndrome or Dravet-like syndrome occur in these genes:
GABRA1GABRA2SCN1BSCN2ACHD2STXBP1 (2)
