Delayed classic and protracted phenotypes of compound heterozygous juvenile neuronal ceroid lipofuscinosis

Objective: To correlate the phenotypes with the genotypes of 10 Finnish juv enile neuronal ceroid lipofuscinosis (JNCL; late-onset Batten disease) pati ents who all are compound heterozygotes for the major 1.02-kb deletion in t he CLN3 gene. Methods: The mutations on the non-1.02-kb deletion chromosome s were screened in 6 patients; in the other 4 patients the mutations were k nown (one affecting a splice site, two missense mutations, and one deletion of exons 10 through 13). Clinical features were examined, and MRI, MRS, so matosensory evoked magnetic field (SEF), and overnight polysomnography (PSG ) studies were performed. Results: A novel deletion of exons 10 through 13 was found in 6 patients belonging to three families. In the patients carryi ng the deletions of exons 10 through 13 the clinical course of the disease- was fairly similar. Variation was greatest in the time course to blindness. In these patients the mental and motor decline was slower than in classic JNCL, but more severe than in the two patients with missense mutations in e xons 11 and 13. MRI showed brain atrophy in 4 patients. One patient had hyp erintense periventricular while matter, otherwise brain signal intensities were normal. SEFs were enhanced in patients older than 14 years, whereas in PSC: all but the youngest 6-year-old patient showed epileptiform activity in slow-wave sleep. Conclusions: JNCL can manifest as at least three differ ent phenotypes: classic, delayed classic, and protracted JNCL with predomin antly ocular symptoms. Finnish compound heterozygotes have the delayed clas sic or the protracted form of JNCL.