Dandy-Walker Malformation, Papillary Thyroid Carcinoma, and SDHD-Associated Paraganglioma Syndrome

Abstract

A 43-year-old female presented to a local hospital with the recent onset of intermittent dizziness suggestive of intermittent rotatory vertigo, but no abnormal findings on examination. Magnetic resonance imaging of the brain demonstrated a large cerebrospinal fluid collection in the posterior fossa, incomplete fusion of the posterior elements of the cerebellum and vermis, and dilatation of the third and lateral ventricles, indicative of a significant Dandy-Walker malformation (Figures 1 and 2). The patient reported a history of papillary thyroid carcinoma diagnosed at 16 years of age and an abdominal paraganglioma diagnosed at the age of 28 in the immediate postoperative period after a cesarean section. Her 2 samples of 24-hour urinary normetanephrine was 10 578 and 19 409 nmol/24 h (normal, 600); the tumor was 4-cm in maximum diameter, I-MIBG positive, and at the level of the lower pole of the right kidney. It was successfully removed. There were no cutaneousfeaturessuggestingahereditarysyndrome.Family history revealed two daughters who had both undergone craniofacial surgery. Genetic analysis demonstrated a pathogenic germline succinate dehydrogenase (SDH) type D mutation (c.60_ 63delGCTT). Further investigation revealed bilateral head and neck paragangliomas at the left jugular foramen and on the right just above the carotid bifurcation; these are currently being considered for therapy. The asymptomatic Dandy-Walker malformation in our patient is an uncommon finding, and few cases have been diagnosed in adults (1). SDHx mutations cause familial paraganglioma syndromes but have also been related to other neoplasias such as renal and pituitary tumors (2) and thyroid cancer (3). It seems probable that SDH may be involved in central nervous system organogenesis as well as acting as a tumor suppressor.