Calista was born in August of 2003 by planned C-Section. When she was born, our first words spoken were, “we already had this baby” as she looked identical to her older sister. Pretty quickly, though, we realized that she was very different, and that something was not quite right. As a newborn, she was extremely sleepy and floppy, and did not cry when she was hungry. We had to set an alarm for every 2 hours around the clock to wake her for feeding, and would go to extremes to keep her awake to finish a feeding. We started bringing concerns to our medical team early on, but were told that we shouldn’t compare her to her older sister as all children are different. Despite this, we continued to voice our concerns at every single appointment.
Calista did not follow a traditional growth course for her height and weight. She was at the 75% for both height and weight from birth up to 13 months of age. However, at 15 months, she dropped to the 50th%. By 26 months, she was at the 5th%. By 68 months, she had only come up slightly to the 10% for height and 20% for weight. At age 10, she moved into the average range for both height and weight. Her head circumference has remained stable and above the norms for her age, at the 98th%.
Almost all of Calista’s developmental milestones were delayed. She continued to sleep an inordinate amount of time - up to 20 hours a day. At Calista’s 12-month well check-up, the doctor noticed the way she was holding her crayon, and referred us for a Neurology consult. The Neurologist ordered an MRI, which was normal, and told us she was probably just a late bloomer, and that we shouldn’t worry. We continued to voice our concerns. At around 18 months, we were concerned that she had plateaued and may have regressed. We advocated for interventions, and she started a strenuous therapy schedule (OT, PT, Speech and an Infant Educator) five days a week. At age 2, she started having horrible rages. We returned to the Neurologist when she was 2-1/2 years old, where again nothing was found and we were told to stop wasting time and money on therapies. We switched Neurologists. The new Neurologist believed she was just developmentally delayed. At age 3, we noticed that she would acquire skills one day and then lose them the next. For example, she was able to count to 10 one day, the next day only to 3. Calista often asked the same questions over and over again. She was shy, but her social skills seemed on target. She was clumsy and fell down a lot. She had a very high pain threshold. One time, she fell and split her front tooth into two pieces; she didn’t cry despite her nerve being completely exposed. Another time, she ran into the leg of a chair and fractured her nose; again she didn’t cry. We continued our quest for answers, going from specialist to specialist and pursuing any test that may give us answers to what was causing our daughter’s issues.
We have observed staring spells for as long as we can remember. Many times, she seemed to “melt away” behaviorally and we just had to leave her alone for her to come out of these episodes. At 3 years old, we enlisted a Neuropsychologist to do an evaluation, and he suggested the “rages” sounded like a type of temporal lobe seizure. The Neurologist disagreed. The Neuropsychologist also noted the up and down performance within each of his sessions with her. A few weeks later, we witnessed Calista’s first generalized convulsive seizure. We suspect this wasn’t the first. She was put on Keppra, but she still had several episodes when her eyes rolled up and she arched her back. At this time, Calista had her first EEG, which showed multifocal epileptiform discharges, as well as very high amplitude spike and wave forms, and it was consistent with a diagnosis of Angelman Syndrome, although the rest of her profile did not support this. Her EEG also showed that she never entered REM sleep and there were no sleep spindles present. Numerous EEGs have followed through the years, and this spike and wave activity has only increased over time, going from being present only during drowsing or sleep states, to being almost constant. At 9 years old, Calista had a MEG study, with findings consistent with Landau Kleffner Syndrome, although the rest of her profile does not support this. During this 50 minute study, Calista had 648 epileptiform spikes. This extraordinarily high level of activity began when she closed her eyes.
She has a polyseizure profile consisting of absence, partial complex, tonic clonic, generalized convulsive, and catamenial. Her convulsive seizures follow a cycle pattern that can last anywhere from 2-5 weeks at a time. Since Calista stops breathing during convulsive episodes, she requires oxygen therapy and has required resuscitation multiple times. She regularly displays mysterious symptoms that come and go. These symptoms follow a cycle pattern, and consist of severe nosebleeds, dizziness, near syncope, deep black rings that suddenly appear under one or both eyes, rapid heart rate at rest, substantial blood pressure fluctuations, and abrupt onset of “not feeling well,” then falling to sleep immediately for hours. Calista's seizures have significantly worsened over time. She has been diagnosed with Borderline Long QT and is monitored annually by a Cardiologist.
Calista has been on numerous anticonvulsants as well as other drugs to try to control her seizures, but she continues to have a refractory profile. The introduction of higher doses or new anticonvulsants have not made substantial improvements; oftentimes the higher doses made her worse. She is very sensitive to medication changes and any new medications are introduced in tiny increments. Medications can appear to provide benefit in the beginning, but then the effectiveness fades (after a honeymoon period). Given the complexity of her regimen and the intricacies of methylation pathways, we have received guidance from a nutritional chemist. Calista’s diet is high potassium, dairy free, casein free, and enriched folate-free. She takes an average of 13 different prescribed medications and carefully titrated supplements daily.
Calista has received many therapeutic (OT, PT, Speech, Music Therapy, Hippotherapy, Vision Therapy, ABA Therapy) and special education interventions all of her life. Due to her extraordinary health issues, Calista now has a specialized in-home school program four days a week - 3 hours a day, with a team of educators and therapists who work closely with us. The flexibility of these professionals has proven vital. Calista experiences good days and bad days and much fluctuation throughout each day. She still sleeps many hours each day - on average 12 hours per night and anywhere from 3 to 8 hours during the day. Her journey has not been easy or predictable. Our goal is to listen as she tries to teach us about her experiences and her needs. She is extremely sensitive to noise and becomes quickly overwhelmed with other stimuli. She has very low stamina and her health status can change in a second - one minute she can appear alert and happy; the next she needs to sleep immediately. Because of this, we make extraordinary modifications in every aspect of her life on a daily basis to give her the best opportunity for success.
In 2013, Calista took part in full genome sequencing through the Idiopathic Diseases of Man (IDIOM) Study at the Scripps Translational Science Institute. The results of this study found that a de-novo variant in KCNB1 was highly likely to be causative of her complex set of conditions. The good news was we finally had an answer; the bad news was there were no previous documented cases in humans. All the research we could find was on lab rats. Since this time, there have been over 80 other individuals diagnosed with KCNB1 around the world. She is currently part of multiple studies to research possible treatments.
Calista is funny, sarcastic, and loveable. She often leaves people speechless with her candid comments and observations. Her favorite things are animals, music and technology. She is never separated from her iPhone, which she uses to listen to music and to send pictures and simple texts using special apps back and forth to her favorite people. Animals enrich her life. Happiness for Calista is anything having to do with animals, technology, Starbucks and FedEx!
Calista has been a true gift to our family. In some ways, she is old beyond her years as she looks at life through such a unique lens. Not a day goes by that we don’t worry about her health and what the future will bring.
We will continue to seek help and even if we get few answers, we will never give up hope that other children will be found, and researchers will join us in our search for a better tomorrow.
As a result of many expert medical evaluations, assessments by neuropsychologists, therapists, educators, and the IDIOM team, the following diagnoses have been identified:
Calista did not follow a traditional growth course for her height and weight. She was at the 75% for both height and weight from birth up to 13 months of age. However, at 15 months, she dropped to the 50th%. By 26 months, she was at the 5th%. By 68 months, she had only come up slightly to the 10% for height and 20% for weight. At age 10, she moved into the average range for both height and weight. Her head circumference has remained stable and above the norms for her age, at the 98th%.
Almost all of Calista’s developmental milestones were delayed. She continued to sleep an inordinate amount of time - up to 20 hours a day. At Calista’s 12-month well check-up, the doctor noticed the way she was holding her crayon, and referred us for a Neurology consult. The Neurologist ordered an MRI, which was normal, and told us she was probably just a late bloomer, and that we shouldn’t worry. We continued to voice our concerns. At around 18 months, we were concerned that she had plateaued and may have regressed. We advocated for interventions, and she started a strenuous therapy schedule (OT, PT, Speech and an Infant Educator) five days a week. At age 2, she started having horrible rages. We returned to the Neurologist when she was 2-1/2 years old, where again nothing was found and we were told to stop wasting time and money on therapies. We switched Neurologists. The new Neurologist believed she was just developmentally delayed. At age 3, we noticed that she would acquire skills one day and then lose them the next. For example, she was able to count to 10 one day, the next day only to 3. Calista often asked the same questions over and over again. She was shy, but her social skills seemed on target. She was clumsy and fell down a lot. She had a very high pain threshold. One time, she fell and split her front tooth into two pieces; she didn’t cry despite her nerve being completely exposed. Another time, she ran into the leg of a chair and fractured her nose; again she didn’t cry. We continued our quest for answers, going from specialist to specialist and pursuing any test that may give us answers to what was causing our daughter’s issues.
We have observed staring spells for as long as we can remember. Many times, she seemed to “melt away” behaviorally and we just had to leave her alone for her to come out of these episodes. At 3 years old, we enlisted a Neuropsychologist to do an evaluation, and he suggested the “rages” sounded like a type of temporal lobe seizure. The Neurologist disagreed. The Neuropsychologist also noted the up and down performance within each of his sessions with her. A few weeks later, we witnessed Calista’s first generalized convulsive seizure. We suspect this wasn’t the first. She was put on Keppra, but she still had several episodes when her eyes rolled up and she arched her back. At this time, Calista had her first EEG, which showed multifocal epileptiform discharges, as well as very high amplitude spike and wave forms, and it was consistent with a diagnosis of Angelman Syndrome, although the rest of her profile did not support this. Her EEG also showed that she never entered REM sleep and there were no sleep spindles present. Numerous EEGs have followed through the years, and this spike and wave activity has only increased over time, going from being present only during drowsing or sleep states, to being almost constant. At 9 years old, Calista had a MEG study, with findings consistent with Landau Kleffner Syndrome, although the rest of her profile does not support this. During this 50 minute study, Calista had 648 epileptiform spikes. This extraordinarily high level of activity began when she closed her eyes.
She has a polyseizure profile consisting of absence, partial complex, tonic clonic, generalized convulsive, and catamenial. Her convulsive seizures follow a cycle pattern that can last anywhere from 2-5 weeks at a time. Since Calista stops breathing during convulsive episodes, she requires oxygen therapy and has required resuscitation multiple times. She regularly displays mysterious symptoms that come and go. These symptoms follow a cycle pattern, and consist of severe nosebleeds, dizziness, near syncope, deep black rings that suddenly appear under one or both eyes, rapid heart rate at rest, substantial blood pressure fluctuations, and abrupt onset of “not feeling well,” then falling to sleep immediately for hours. Calista's seizures have significantly worsened over time. She has been diagnosed with Borderline Long QT and is monitored annually by a Cardiologist.
Calista has been on numerous anticonvulsants as well as other drugs to try to control her seizures, but she continues to have a refractory profile. The introduction of higher doses or new anticonvulsants have not made substantial improvements; oftentimes the higher doses made her worse. She is very sensitive to medication changes and any new medications are introduced in tiny increments. Medications can appear to provide benefit in the beginning, but then the effectiveness fades (after a honeymoon period). Given the complexity of her regimen and the intricacies of methylation pathways, we have received guidance from a nutritional chemist. Calista’s diet is high potassium, dairy free, casein free, and enriched folate-free. She takes an average of 13 different prescribed medications and carefully titrated supplements daily.
Calista has received many therapeutic (OT, PT, Speech, Music Therapy, Hippotherapy, Vision Therapy, ABA Therapy) and special education interventions all of her life. Due to her extraordinary health issues, Calista now has a specialized in-home school program four days a week - 3 hours a day, with a team of educators and therapists who work closely with us. The flexibility of these professionals has proven vital. Calista experiences good days and bad days and much fluctuation throughout each day. She still sleeps many hours each day - on average 12 hours per night and anywhere from 3 to 8 hours during the day. Her journey has not been easy or predictable. Our goal is to listen as she tries to teach us about her experiences and her needs. She is extremely sensitive to noise and becomes quickly overwhelmed with other stimuli. She has very low stamina and her health status can change in a second - one minute she can appear alert and happy; the next she needs to sleep immediately. Because of this, we make extraordinary modifications in every aspect of her life on a daily basis to give her the best opportunity for success.
In 2013, Calista took part in full genome sequencing through the Idiopathic Diseases of Man (IDIOM) Study at the Scripps Translational Science Institute. The results of this study found that a de-novo variant in KCNB1 was highly likely to be causative of her complex set of conditions. The good news was we finally had an answer; the bad news was there were no previous documented cases in humans. All the research we could find was on lab rats. Since this time, there have been over 80 other individuals diagnosed with KCNB1 around the world. She is currently part of multiple studies to research possible treatments.
Calista is funny, sarcastic, and loveable. She often leaves people speechless with her candid comments and observations. Her favorite things are animals, music and technology. She is never separated from her iPhone, which she uses to listen to music and to send pictures and simple texts using special apps back and forth to her favorite people. Animals enrich her life. Happiness for Calista is anything having to do with animals, technology, Starbucks and FedEx!
Calista has been a true gift to our family. In some ways, she is old beyond her years as she looks at life through such a unique lens. Not a day goes by that we don’t worry about her health and what the future will bring.
We will continue to seek help and even if we get few answers, we will never give up hope that other children will be found, and researchers will join us in our search for a better tomorrow.
As a result of many expert medical evaluations, assessments by neuropsychologists, therapists, educators, and the IDIOM team, the following diagnoses have been identified:
- KCNB1 Genetic Mutation Impacting K+ Channels
- Epileptic Encephalopathy
- Complex Partial Seizure Disorder/ Epilepsy – polyseizure profile: Convulsive and Non-Convulsive type, Generalized Seizures intermittent, Catamenial Epilepsy
- Major Neurocognitive Disorder due to multiple etiologies with Behavioral Disturbance
- Unspecified Brain Disorder
- Very early left-sided Mesotemporal Sclerosis (subtle asymmetric volume loss without abnormal T2 hyperintensity involving the left hippocampus)
- Hypoxic events secondary to convulsive seizures
- Cerebral Folate Deficiency Syndrome
- MTRR Genetic Mutation
- Positive for Narcolepsy genetic markers
- Chronic migraine with aura
- Dysarthria, a neuromotor disorder negatively impacting speech due to poor oral motor control and coordination, speech production, breath control, saliva control, range of motion of her tongue, and chewing skills
- Dyspraxia, a neuromotor disorder negatively impacting fine and gross motor coordination and motor planning
- Mild Trendelenburg
- Mild Lordosis
- Reduced Reflexes in Upper and Lower Extremities
- Bilateral Ptosis
- Developmental Dyscoordination Disorder
- Receptive and Expressive Aphasia / Moderate Receptive and Expressive Language Disorder
- Hypotonia
- Myopathy: Type 1 Fiber Predominance with mild generalized hypertrophy
- Vasospams impacting blood pressure and may cause abrupt drops/”fainting” episodes
- Borderline Long QT per established EKG standards
- CNS Disorder
- Dopamine Dysregulation
- Difficulty at Midline
- Excessive Daytime Sleepiness
- Right Sided Weakness
- Some features of Autism Spectrum Disorder
- Hyperacusis with pain, and left ear weakness in dichotic listening situations; experiences auditory fatigue
- Constipation secondary to functional bowel muscle weakness
- Decreased urine output of unknown derivation; has risk of dehydration due to fluid intake that is below age norms
- Hyperopic Refraction, Exotropia, Divergence Excess, Accommodative Dysfunction, Hypertropia, Oculomotor Dysfunction in Pursuits and Saccades, Visual Perceptual Dysfunction, and Visual Motor Integration Dysfunction.
- Below Average Cognitive Performance on Standardized Measurements