GE-13 * A NOVEL ASSOCIATION OF PRIMARY CNS GERMINOMA IN A PATIENT WITH NAIL PATELLA SYNDROME

Abstract

Nail patella syndrome (NPS) is an autosomal dominant disorder with a prevalence of 1/50,000 characterized by developmental abnormalities of the nails, knees and elbows, as well as renal dysplasia and open angle glaucoma. NPS is caused by a mutation in the LMX1B gene, a transcription factor involved in ventral/dorsal patterning of the vertebrate limb. While malignancy is rare in patients with NPS, Ewing's sarcoma and colon cancer have been reported. Additionally, NPS has been described in a 5 generation family with neurofibromatosis type 1. We report a novel association of NPS with primary CNS germinoma. A 22-year-old male presented with a two-month history of diabetes insipidus (DI) and headaches. Physical examination revealed partial Parinaud's syndrome, dystrophic nails and surgical repair of left hypoplastic patella. Because the family history revealed numerous maternal family members with dystrophic nails and hypoplastic patellae, we subsequently made a formal clinical diagnosis of NPS. Contrast enhanced MRI of the brain revealed an enhancing cystic pineal mass and a Chiari I malformation; serum and CSF alpha-fetoprotein and beta-human chorionic gonadotropin were negative. Biopsy of the pineal mass was consistent with pure germinoma for which the patient received external beam radiation therapy via intensity modulated radiation therapy (IMRT) as follows: 1) 2520 cGy to the craniospinal axis; 2) 5040 cGy to the pineal region; 3) and 4620 cGy to the suprasellar region (for presumed tumor in the posterior pituitary given the history of DI). He remains in remission 9 years post-treatment. For the NPS, the patient declined referral to genetics due to insurance concerns but he and his family have been referred to appropriate services for screening of other abnormalities associated with the syndrome. This case report suggests that LMX1B may play a role in the development of CNS germinoma.