How Common Are Seizures in Holoprosencephaly?

Seizures are very common in children with holoprosencephaly (HPE), affecting approximately 50% of those diagnosed with the condition ^[1]. The likelihood and severity of seizures often correspond to the severity of the brain malformation. While they are most frequent in severe forms like alobar HPE (where the brain has not divided at all), they can also occur in semilobar (partial division) and lobar HPE (where the brain is mostly divided, the least severe form) ^[1][2][3]. Because seizures are a direct result of the structural differences in your child’s brain, early recognition and treatment are critical parts of managing HPE.

(Note: While this guide primarily focuses on children, as HPE is diagnosed at birth or in infancy and seizures most commonly start in childhood, adults with milder forms of HPE may also experience epilepsy and require similar management strategies.)

Recognizing Seizures and Infantile Spasms

In babies and young children with structural brain differences like HPE, seizures can sometimes be difficult to recognize because they may present with subtle or unusual signs ^[4][5]. Parents should closely watch for a specific type of seizure called infantile spasms, a medical emergency that requires immediate specialized treatment.

Signs of infantile spasms and other seizures include:

• “Jackknife” movements: Sudden, brief stiffening where the baby’s head drops forward and their arms and legs fling outward or pull inward toward their chest ^[6][7].
• Clustering: Infantile spasms typically occur in groups or “clusters” (one right after another), very often when the baby is just waking up or falling asleep ^[6][7].
• Asymmetrical movements: In children with structural brain differences, spasms may look uneven, with one side of the body moving more than the other ^[8].
• Focal signs: You may notice rhythmic jerking of just one arm or leg, fixed staring with eyes deviated to one side, or repetitive “automatic” movements like lip-smacking or rhythmic sucking ^[9][4].
• Autonomic changes: Sometimes, the only outward sign of a seizure in a baby is a sudden change in their breathing pattern, heart rate, or skin color (such as turning pale or blue) ^[4].

Actionable tip: If you see any unusual, repetitive movements that you suspect might be a seizure, capture them on video with your smartphone. Video evidence is incredibly helpful for neurologists to quickly diagnose the type of seizure and begin the correct treatment ^[6].

Seizure Safety and First Aid

Because children with HPE are at high risk for seizures, it is important to be prepared at home. Work with your neurologist to create a formal Seizure Action Plan. This plan outlines exactly what to do during a seizure and when to use at-home rescue medications (often a fast-acting drug like a benzodiazepine) for seizures that will not stop on their own ^[10][11].

If your child has a seizure, follow basic first-aid steps:

• Stay calm and time the seizure: Note exactly when the seizure starts and ends.
• Keep them safe: Roll your child gently onto their side to help keep their airway clear. Remove any nearby objects that could cause injury.
• When to call 911: Seek emergency medical care if a seizure lasts longer than 5 minutes, if your child has difficulty breathing or remains unresponsive after the seizure, or if they experience multiple seizures in a row without waking up in between ^[12][10].

Treatment Options and Challenges

The medical management of seizures in children with HPE generally follows the standard protocols used for other pediatric brain malformations ^[1].

• First-Line Medications: Treatment typically begins with standard anti-seizure medications (ASMs) chosen for your child’s specific seizure type ^[13]. However, if your child is diagnosed with infantile spasms, standard ASMs are usually ineffective. Instead, they will require unique first-line therapies such as hormonal treatments (like ACTH or high-dose oral corticosteroids) or specific targeted medications like vigabatrin ^[14][15].
• Refractory (Drug-Resistant) Epilepsy: Because the seizures in HPE are caused by structural differences in the brain, they can sometimes be “refractory,” meaning they are hard to control ^[13]. Epilepsy is officially considered drug-resistant if two appropriately chosen and tolerated medications have failed to stop the seizures ^[16][17].
• Combination Therapies: If a single medication does not work, your care team will likely prescribe a combination of medications ^[16]. If medications continue to fail, they may discuss alternative therapies. These can include specialized diets (like the ketogenic diet, which fundamentally changes how the brain uses energy to reduce seizure activity) or neurostimulation devices like Vagus Nerve Stimulation (VNS), which sends mild electrical impulses to the brain ^[13][18].

Witnessing your child have a seizure is frightening, but knowing what to look for, establishing a safety plan, and working closely with a pediatric neurologist or epileptologist will ensure you are prepared to manage this common complication of HPE.