Associated Conditions
There is no single way IMPDH2-related disorders present.
“IMPDH2-related disorders” is rare. It is a string of seemingly random letters and a number. When you search for information about what to expect it is easy to become disheartened by the lack of information.
When Sebastian received his diagnosis we already knew he had global developmental delays and needed physical therapy. We suspected he had cerebral palsy. While researching cerebral palsy we learned about cerebral visual impairment (CVI) and immediately recognized many of the signs in Sebastian. Over time these diagnoses were confirmed and we learned about other conditions affecting him.
We call these associated conditions.
Associated conditions are medical conditions that have been reported in people with IMPDH2-related disorders and are believed to be linked to the genetic alteration. Some of the conditions described on this page are conditions we know personally through Sebastian's experience. Others have been reported in other people with IMPDH2 genetic variants.
Not everyone with an IMPDH2 genetic variant will experience the same conditions. There is no single list of symptoms that applies to everyone. Part of what makes these disorders so difficult to understand is that we are still learning how they can affect different people.
Receiving a diagnosis is hard. But sometimes an official diagnosis can help open doors that your child needs opened.
For example, we first heard the words “it might be cerebral palsy” months before Sebastian's first seizure. At the time the possibility of CP was devastating. Less than a year later we were prepared to fight for him to receive the diagnosis.
“IMPDH2-related disorders” does not mean anything to the broader medical community. Many healthcare providers will never encounter it. Insurance systems and therapy programs don’t have a specific code for the genetic condition. This could impact Sebastian’s ability to access support systems. Cerebral palsy is well known. Sebastian's developmental and motor challenges fit within the broad definition of CP. He greatly benefits from therapies and services designed for children with CP. Having a diagnosis that healthcare providers, therapists, schools, and insurance systems recognize can make it easier to access the support a child needs.
We recommend you review the below information for informational purposes only - we’re certainly not qualified to be handing out medical advice! Please discuss medical concerns, symptoms, testing, treatments, and medications with your child's healthcare team.
Dystonia
Dystonia (Dystonic Muscle Tone)
The majority of individuals diagnosed with a variant in the IMPDH2 gene have dystonia. Dystonia is a movement disorder that causes muscles to tighten or contract without a person wanting them to. This can make parts of the body twist, turn, or move into unusual positions. It may also cause shaking or repeated movements. Some people have dystonia all the time, while others only have it during certain activities or when they are tired, excited, or stressed. Dystonia can affect one part of the body or many parts. It is caused by the brain sending the wrong signals to the muscles—it is not something the person can control or stop by trying harder.
It was hard for us to really understand dystonia and a year later we’re still learning about this condition. Sebastian’s dystonia has primarily appeared as leg twisting or repetitive arm movements. It has caused extreme muscular pain and also severe constipation, also causing pain. It comes on stronger when he is tired or feeling emotional. At two years old Sebastian is making amazing progress walking with assistance. But dystonia in his torso makes it difficult for him to fully control his movements and affects his confidence. We’re very grateful to have found a medication that significantly increases his ability to control his muscles and movements.
Cerebral Palsy
The most common childhood motor disorder is cerebral palsy (often shortened to CP). CP is a condition that affects movement, balance, posture, and muscle control. It is caused by differences in the development or function of the brain, most commonly due to an oxygen deprivation event. The definition expanded in recent years to include genetic alterations as a cause. The extent to which CP impacts an individual greatly varies.
Cerebral palsy was one of the first diagnosis we heard theorized in our early medical days. CP impacts Sebastian’s gross motor skills, fine motor skills, and speech capabilities. He greatly benefits from physical therapy, occupational therapy, speech therapy, and aquatics therapy.
Cerebral/Cortical Visual Impairment
What does a brain-based visual impairment even mean? Cerebral visual impairment, often called CVI, affects the way the brain processes visual information. A person with CVI may have healthy eyes but still have difficulty making sense of what they see. The exact impact varies person to person but some examples of challenges include recognizing faces, finding objects, noticing objects in a busy or cluttered environment, judge distance, and use vision consistently. It can lead to sensory challenges as well. CVI is different from a problem with the eyes themselves. A child may have normal or near-normal eye structures and still have significant difficulty using vision. Many children with CVI benefit from strategies, therapies, and environmental changes that help make visual information easier for the brain to process.
Sebastian’s primary doctor referred him to ophthalmology at four months because he was not holding eye contact or visually tracking objects. After his first seizure, as we began going down rabbit holes trying to understand cerebral palsy, Jake discovered CVI. It fit Sebastian to a tee. We knew he could distinguish light from dark because he needed dark to sleep. Occasionally it seemed like he made brief eye contact. And he had passed the 20/20 vision screening test. But we knew he could not see the way our other boys could. Fortunately his occupational therapist was incredibly knowledgable about CVI and helped us learn strategies immediately. We had to teach Sebastian’s brain that yes, he is seeing things. It’s amazing how many things vision impacts. As his visual skills improved we began seeing so many milestones start to unlock: reaching, rolling, feeding himself, and more.
There are so many ways you can start incorporating vision therapy into your routines today if you suspect your child has CVI. Check out the resources for more information.
Epilepsy
Epilepsy is a neurological condition that causes repeated, unprovoked seizures due to sudden bursts of abnormal electrical activity in the brain. Seizures can look very different from person to person. Some involve full-body movements, others may affect only one side of the body, and some seizures may be subtle and involve changes in awareness, movement, behavior, or responsiveness.
Seizures can be scary to witness, especially the first time you see one. If you believe your child is having a seizure, stay calm and focus on keeping them safe. Call 911 for assistance and direct instructions. If possible record a video - this can be extremely helpful for neurologists and medical professionals to assess exactly what happened.
Sebastian's first seizure was febrile, meaning it occurred with a fever. Thanks to an incredible emergency department doctor, that seizure became the beginning of our diagnosis journey. He has experienced multiple seizures since, some febrile and some unprovoked. We have found success working with his neurology team and his seizures can be managed with medication.
One additional condition we believe may be associated with Sebastian's seizures is central apnea. Central apnea occurs when the brain temporarily stops sending the signals needed to breathe. Sebastian has experienced episodes in which he stopped breathing for 10 to 30 seconds and then appeared to enter a postictal state—the period of recovery that can follow a seizure. It took four months of these episodes occurring multiple times every few weeks before one was captured on a monitor in the emergency department. Obviously this was an extremely trying time for our family. The central apnea diagnosis is the clearest example we have of the challenges of a rare genetic condition - the responsibility of figuring out patterns, explaining concerns over and over, and keeping our child safe fell completely on us. We now know one or two others in our IMPDH2 community who also experience central apnea - the more we can learn from our collective experiences, the better it will be for the future.
Feeding Concerns
Feeding difficulties look different for each kid. For some babies feeding challenges are noticed early through difficulty nursing or taking a bottle. For other children issues may become more apparent later, such as difficulty eating a wide variety of foods or maintaining expected growth.Some children in our IMPDH2 community eat entirely by mouth and some rely on g-tubes for nourishment.
This was the first signal that Sebastian had medical challenges ahead of him. He struggled to return to birth weight - while he could latch and suck he did not have the motor control to swallow milk. Because of this his first trip to neurology occurred at 17 days old. He ended up passing the exam that day but feeding concerns have followed him ever since. Currently he self-feeds entirely by mouth but has struggled to gain weight in the past six months.
Strabismus
Strabismus is a condition in which the eyes do not always point in the same direction. It is sometimes called a wandering eye or crossed eyes, depending on how the eyes are affected. One eye may turn inward, outward, upward, or downward. It can affect how a person uses both eyes together and often impacts depth perception. Genetic alterations in the IMPDH1 gene are known to affect vision. As you may guess from the names, the IMPDH1 gene is closely related to the IMPDH2 gene, which may explain why several children have various vision concerns.
Sebastian will likely need surgery to correct this. For now he wears low-prescription glasses as part of an effort to strengthen the alignment of his eyes without surgery.
Other Associated Conditions
The conditions listed above are the ones we know personally through Sebastian's experience. But that is not a complete picture of how we believe IMPDH2 related disorders can present. We know that dystonia and epilepsy are common associated conditions. But there is no single way the condition present. Some other conditions reported in people with IMPDH2-related disorders include:
Apraxia of Speech
A motor speech disorder that makes it difficult for the brain to plan and coordinate the movements needed for speaking.
Autism
A neurodevelopmental condition that can affect communication, social interaction, sensory processing, behavior, and the way a person experiences the world.
Central Auditory Processing Disorder
A condition in which the brain has difficulty processing or making sense of sounds, even when a person's hearing is otherwise normal.
Heart Conditions
Some parents have been told that heart conditions may be associated.
Low Muscle Tone
Also called hypotonia, low muscle tone means that the muscles have less tension than expected. It can affect posture, movement, strength, and motor development.
Nystagmus
Involuntary, repetitive eye movements. The eyes may move from side to side, up and down, or in another repeated pattern.
We’re all still learning. As more people are diagnosed and more research is conducted our understanding of IMPDH2-related disorders will continue to grow.