Ryan Rilinger1, Joyce Lee2, Nayef Kiame2, Lamis Yehia3, Ying Ni4, Robert Wilson5, Andrew Dhawan6
1Cleveland Clinic Lerner College of Medicine, 2Case Western Reserve University School of Medicine, 3Epilepsy Center, Neurological Institute, 4Department of Cancer Sciences, Cleveland Clinic Research, 5Department of Neuromuscular Medicine, 6Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic
Objective:
We characterize the prevalence of dysautonomia in a large single-center cohort of patients with PTEN hamartoma tumor syndrome (PHTS) and examine the association between genomic variants in PTEN and syndrome phenotypes.
Background:
PHTS encompasses cancer and overgrowth predisposition syndromes caused by pathogenic germline PTEN variants. Clinically, symptoms of dysautonomia have been noted in PHTS; however, it is not known if PHTS is itself associated with dysregulation of the autonomic nervous system at a frequency higher than the general population. Characterizing the prevalence and phenotype of dysautonomia among patients with PHTS may inform our understanding of this disease.
Design/Methods:
184 patients diagnosed with PHTS via germline PTEN pathogenic variant presence, seen for care between 2008 and 2024, were included. Retrospective chart review identified PTEN variant details, oncologic and autism spectrum disorder (ASD) history, and 15 symptoms common in dysautonomia. All symptoms for which another etiology was identified were excluded. Symptoms were classified into four general organ systems: gastrointestinal, neurosensory, cardiovascular, and thermoregulatory.
Results:
75% of the cohort had at least one symptom of dysautonomia not attributable to another cause. Patients with PHTS and a cancer diagnosis, compared to those without cancer, demonstrated a significantly greater prevalence of autonomic symptoms affecting the cardiovascular system (21.7% vs. 7.3%, p = 0.010) and thermoregulatory function (31.7% vs. 10.7%, p <0.001). These patients demonstrated a higher prevalence of palpitations, dry eye, and temperature dysregulation. Patients with ASD were significantly less likely to display thermoregulatory symptoms (5.7% vs. 22.1%, p = 0.009). No specific PTEN gene variant classes or effects demonstrated an altered risk of dysautonomia.
Conclusions:
Patients with PHTS and malignancy demonstrate higher prevalence of cardiovascular and thermoregulatory dysautonomia, whereas patients with PHTS and ASD display less thermoregulatory dysfunction. Additional research is needed to determine whether features of dysautonomia precede oncologic diagnosis in PHTS.
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