Authors :
Presenting Author: Rozalia Valentine, MS CGC – DYNC1H1 Association and TUBB2A Foundation
Sonal Mahida, MS CGC – Boston Children's Hospital
Lacey Smith, MS, CGC – Boston Children's Hospital
Beth Sheidley, MS, CGC – Boston Children's Hospital
Lauren LaFortune, MD – Boston Children's Hospital
Chellamani Harini, MD – Boston Children's Hospital
Christelle Moufawad El Achkar, MD – Boston Children's Hospital
Heather Olson, MD, MS – Boston Children's Hospital
Sanjay Prabhu, MBBS, FRCR – Boston Children's Hospital
Rozalia Valentine, MS, CGC – Associated with DYNC1H1 Association
Rationale:
ARID1B variants are a common cause of intellectual disability and the most common cause of Coffin Siris syndrome, a syndromic neurodevelopmental disorder. Up to 30% of patients with ARID1B-related disorders (ARID1B-RD) have epilepsy. Structural brain abnormalities are seen in 30-40% of patients, with the most common finding being hypoplasia or agenesis of the corpus callosum. However, focal cortical dysplasias (FCDs) were not previously reported in ARID1B-RD.
Methods:
We conducted a literature review for studies of ARID1B-RD between 1993-2024. We performed a retrospective chart review of two patients with ARID1B-RD and FCDs identified at Boston Children’s Hospital.
Results:
Out of 77 relevant papers on ARID1B-RD, none reported FCDs as an imaging finding. We reviewed two patients with pathogenic truncating variants in ARID1B, clinical presentations consistent with a diagnosis of ARID1B-RD, and multifocal FCDs.
Patient 1 presented at 18 months with multiple seizure types, including epileptic spasms, tonic, myoclonic, and subclinical seizures. Neuroimaging identified a large region of FCD involving the left superior and middle frontal gyri, along with smaller FCDs in the left frontal operculum and medial right temporal lobe. Seizures remained medically refractory, EEGs captured clusters of epileptic spasms with diffuse or left-sided onset, and PET demonstrated decreased FDG uptake in the left frontal lobe. At 47 months, she underwent a palliative left frontal disconnection. Pathology confirmed FCD type Ib. At last follow-up, she remained seizure-free 16 months post-surgery.
Patient 2 was diagnosed with seizures at three years, initially presenting with “staring episodes” and centrotemporal spikes on EEG. Neuroimaging revealed multifocal areas of focal cortical dysplasia involving the right frontal, parietal, and occipital lobes. After good seizure control, she was weaned off medication. She re-presented at 15 years of age with intermittent episodes of rightward eye deviation. EEG captured brief generalized seizures, with diffuse 3-4 Hz spike and wave discharges correlating with eye closure and behavioral arrest. At last follow-up at 17 years of age, seizures were well-controlled on lamotrigine monotherapy.
Conclusions:
We present two individuals with ARID1B-RD, epilepsy, and multifocal FCDs, a previously unreported MRI finding in ARID1B-RD. For one patient, the identification of the FCDs led to surgery with subsequent seizure freedom. For the second patient, EEG was suggestive of a generalized epilepsy and seizures are well-controlled. These cases illustrate the complex interplay between FCDs and epilepsy in ARID1B-RD and underscore the importance of detailed neuroimaging, as the identification of FCDs may have critical implications for clinical management in a subset of patients. We propose that dedicated neuroimaging to evaluate for FCDs should be considered in patients with ARID1B-RD and drug-resistant epilepsy.
Funding: none