Improving Early Detection of CDKL5 Deficiency Disorder in Infants

CDKL5 Deficiency Disorder (CDD) often begins with seizures in the first months of life. Pediatric neurologists frequently see these patients early, identify infantile spasms and begin treatment. Yet clinicians can miss the underlying diagnosis. Inconsistent clinical features and reliance on phenotype alone can obscure CDD, delaying access to targeted therapies and coordinated care that can improve long-term outcomes.

Aynara Wulsin, MD, PhD, a pediatric epileptologist who specializes in epilepsy genetics at Cincinnati Children’s, cares for patients with CDD at the Vinaya Rett Syndrome and Related Spectrum Disorders Clinic. Cincinnati Children’s is one of 11 programs nationally designated as a CDD Center of Excellence for its expertise in multidisciplinary care and research.

“Some infants with CDD don’t show classic EEG findings associated with infantile spasms, such as hypsarrhythmia,” Wulsin said. “As a result, infantile spasms may not be recognized initially, leading to delays in diagnosis and initiation of appropriate therapies.”

Exome or genome sequencing testing is essential. Cincinnati Children’s offers a comprehensive gene sequencing analysis that includes testing for CDD.

Diagnosis Directly Impacts Treatment Decisions

A definitive diagnosis paves the way for targeted treatment.

Seizures associated with CDD are typically generalized and can appear in many different forms. Seizures are frequent, severe and very often treatment resistant. Drugs that are effective for specific seizure types, including infantile spasms, don’t work as well in children with CDD. Research suggests that certain medications may be more effective in CDD. In 2022, the FDA approved ganaxolone for CDD-related generalized motor seizures based on the drug’s efficacy. Fenfluramine and cannabidiol have also shown some evidence of seizure reduction in smaller, open-label studies.

In addition to prioritizing evidence-based anti-seizure therapies, Wulsin and her colleagues often pursue early evaluation for epilepsy surgery—specifically, vagus nerve stimulation or corpus callostomy. Newer data suggests that earlier implantation can improve seizure control and provide long-term benefits.

“We know that treating seizures early gives patients the best chance to reach their cognitive and neurodevelopmental potential,” she said. “It does not change the underlying diagnosis, but it can help improve quality of life for both patients and their families.”

Coordinated Care for Complex Needs

Although seizures are one of the main morbid factors of CDD, the disease affects multiple systems, including motor function, sleep, nutrition and respiratory health. Treatment of CDD within Cincinnati Children’s Rett Clinic operates as a true coordinated model where specialists in neurology, genetics, rehabilitation, developmental pediatrics, nutrition and therapy services offer disease-specific expertise.

“A common misconception is that rare conditions can be effectively managed through standard, fragmented subspecialty care models,” Wulsin said. “In reality, optimal care requires coordinated multidisciplinary expertise and dedicated clinical infrastructure. That’s challenging for any institution since CDD is so rare. But it makes a huge impact on patients and their families.”

A Model Designed for Co-Management

Patients with CDD typically see Wulsin at least four times a year depending on their seizure severity. They have a comprehensive, one-day visit with multiple specialists in the CDD clinic once or twice a year.

For patients who receive their primary neurological care elsewhere, they can come for multidisciplinary visits at regular intervals, while their local neurologist continues to manage day-to-day needs. “That partnership is essential,” says Wulsin, “especially for families who live far from a specialty center.”

Advancing the Future of CDD Care

The Rett Clinic and related disorders at Cincinnati Children’s opened in 2013 and has participated in a national CDD registry for many years. The new Center of Excellence designation expands opportunities to participate in emerging gene therapy research. “We are entering a transformative era in epilepsy genetics and in CDD in particular, where therapies designed to target the underlying cause of disease are becoming a reality,” said Wulsin. “Our center is committed to helping lead this next phase of care by ensuring these innovative therapies are rigorously studied and delivered safely and effectively.”

Learn more about the Vinaya Rett Syndrome and Related Spectrum Disorders Clinic.

(Published June 2026)

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