Central nervous system, cranial, and cerebrovascular conditions beyond the Kimonis criteria in patients with Gorlin syndrome: a retrospective cohort study.

Abstract

Background: Gorlin syndrome is a multisystem developmental and cancer-predisposing disorder commonly caused by germline PTCH1 variants. The Kimonis clinical criteria capture the canonical phenotype; however, central nervous system (CNS), cranial, and cerebrovascular conditions documented beyond these criteria remain poorly defined.

Methods: We conducted a retrospective descriptive cohort study of 32 patients who fulfilled the Kimonis clinical criteria and received care at either or both hospitals in Japan. Clinical information through March 31, 2026, including sufficiently documented care elsewhere, was reviewed. The exploratory primary descriptive outcome was defined as the presence of at least one documented condition in three categories: structural CNS or cranial conditions, cerebrovascular disorders, or CNS neoplasms other than medulloblastoma. The three categories were considered separately.

Results: A PTCH1 sequence variant or whole-gene deletion was documented in 24 of 32 patients. Eight patients had 10 documented findings representing eight conditions, including hydrocephalus, Chiari malformation, syringomyelia, moyamoya disease, and cerebral infarction. These findings were identified during routine longitudinal clinical care rather than systematic neuroimaging screening and therefore should not be interpreted as a prevalence estimate. Four patients underwent neurosurgical or cerebrovascular interventions.

Conclusion: Clinically relevant CNS, cranial, and cerebrovascular conditions documented beyond the Kimonis criteria may warrant consideration when new neurological, respiratory, or craniocervical symptoms arise. Awareness of these conditions may inform symptom-directed differential diagnosis and the selection of imaging modalities and anatomical coverage. These exploratory findings do not establish a unified neurological phenotype or causal relationship with Gorlin syndrome and do not support universal neuroimaging surveillance in asymptomatic patients.