Primrose syndrome is a rare, slowly progressive genetic disorder that can vary symptomatically between individual cases, but is generally characterised by ossification of the external ears, learning difficulties, and facial abnormalities. It was first described in 1982 in Scotland's Royal National Larbert Institution by Dr D.A.A. Primrose. Primrose syndrome appears to occur spontaneously, regardless of family history. The cause is currently unknown and there are no known treatments. Signs and symptoms The common symptoms in all reported cases of primrose syndrome include ossified pinnae, learning disabilities or intellectual disability, hearing problems, movement disorders (ataxia, paralysis, and parkinsonism among others—likely due, in part, to calcification of the basal ganglia), a torus palatinus (a neoplasm on the mouth's hard palate), muscle atrophy, and distorted facial features. Other symptoms usually occur, different in each case, but it is unknown whether or not these symptoms are caused by the same disease. Pathophysiology The cause of Primrose syndrome is currently unknown. This condition is extremely rare and seems to spontaneously occur, regardless of family history. In the case studied by Dalai et al. in 2010, it was found that an abnormally high amount of calcitonin, a hormone secreted by the thyroid gland to stabilize blood calcium levels, was present in the blood serum. This suggests that the thyroid gland is releasing an abnormal amount of calcitonin, resulting in the disruption of calcium level homeostasis. No molecular cause was found, but an expanded microarray analysis of the patient found a 225.5 kb deletion on chromosome 11p between rs12275693 and rs1442927. Whether or not this deletion is related to the syndrome or is a harmless mutation is unknown. The deletion was not present in the patient's mother's DNA sample, but the father's DNA was unavailable. Diagnosis Management Currently there are no known treatments. History There have been very few reported cases of Primrose syndrome worldwide. The first known case was described by D.A. Primrose in 1982. The patient was a 33-year-old intellectually disabled male whose outer ears had ossified. Additional symptoms included muscle atrophy in the legs and hands, deafness, cataracts, and a tissue mass covering the roof of his mouth. In 1986, Calacott et al. described a mentally disabled patient whose pinnae had ossified. The patient also experienced deafness, cataracts, skeletal deformities, and muscle atrophy. As the second reported case of such symptoms, it suggested that these symptoms were part of one entity, named "Primrose syndrome"