Finland and the Finns have been the subject of numerous genetic and genealogical studies, owing to enrichment of certain rare hereditary disorders in the Finnish population. Two types of NCL have so-far been found almost exclusively in Finland: Finnish variant late infantile NCL,
vLINCL (CLN5), and the
Northern epilepsy syndrome or Progressive
epilepsy with
mental retardation, EPMR (CLN8). The first symptoms of
Finnish vLINCL are concentration problems or motor clumsiness by 3 to 6 years of age, followed by
mental retardation, visual failure,
ataxia,
myoclonus, and
epilepsy.
Northern epilepsy, the newest member of the NCL family with the most protracted course, is characterized by the onset of
generalized seizures between 5 and 10 years of age and subsequent progressive
mental retardation. Visual problems are slight and late, while
myoclonus has not been observed. Both the
Finnish vLINCL and
Northern epilepsy are pathologically characterized by intraneuronal cytoplasmic deposits of autofluorescent granules which are
Luxol fast blue-, PAS-, and
Sudan black B-positive in
paraffin sections. In
Northern epilepsy the intraneuronal storage process and neuronal destruction are generally of mild degree but highly selective and, in contrast to other forms of childhood onset NCL, the cerebellar cortex is relatively spared. By electron microscopy the storage bodies mainly contain rectilinear complex type and fingerprint profiles in
Finnish vLINCL and structures resembling curvilinear profiles in
Northern epilepsy.
Mitochondrial ATP synthase subunit c is the main stored
protein in both disorders. Both the DCLN5 and CLN8 genes encode putative
membrane proteins with yet unknown functions. Furthermore, a well studied spontaneously occurring autosomal recessive mouse mutant, motor neuron degeneration (mnd) mouse, is a homolog for CLN8.