Two new patients with Curry-Jones syndrome with trichoblastoma and medulloblastoma suggest an etiologic role of the sonic hedgehog-patched-GLI pathway

Abstract

Curry–Jones syndrome (OMIM #601707) is a rare multiple malformation disorder of unknown etiology, associated with brain and skull abnormalities, polysyndactyly, and defects of the eyes, skin and gastrointestinal tract. We report on two new cases of Curry–Jones syndrome with previously unreported features, including benign and malignant neoplasms. The first patient had typical features of Curry–Jones syndrome as well as multiple intra‐abdominal smooth muscle hamartomas and trichoblastoma of the skin. The second patient was born with occipital meningoceles and developed a desmoplastic medulloblastoma. Routine lymphocyte karyotype, GLI3 gene analysis and Patched (PTCH) gene analysis on both patients and chromosome microarray analysis on the first patient were normal. We review the previously reported cases of Curry–Jones syndrome and compare our patients' findings. In view of the association of trichoblastoma with basal cell carcinoma and desmoplastic medulloblastoma with nevoid basal cell carcinoma syndrome (NBCCS) and PTCH mutations, we hypothesize that Curry–Jones syndrome is caused by malfunction of an element in the sonic hedgehog pathway.