Electroclinical spectrum of the neuronal ceroid lipofuscinoses associated with CLN6 mutations

Abstract

In all patients, multifocal myoclonic jerks and seizures were a key feature, but myoclonic seizures were an early and prominent sign in the teenage/adult form only. Conversely, the childhood-onset form was characterized by initial and severe cognitive impairment coupled with electroretinogram and EEG attenuation. Cortical hyperexcitability, shown by the PPR and enlarged somatosensory evoked potentials, was a universal feature.

The Spectrum of Movement Disorders in Childhood‐onset Lysosomal Storage Diseases

“…It is important to recognize that movement disorders, although not a presenting symptom in our patients, are among the most frequent initial symptoms, particularly in adolescents and adults, where a combination of two or more movement disorders, or a combination of psychiatric symptoms and movement disorders, should raise suspicion for NPC or other less common LSD, such as Tay‐Sachs disease . CLN6, a “variant” late infantile‐onset from of NCL, is characterized by developmental delay and regression, vision loss, seizures, myoclonus, as well as cerebellar dysfunction with ataxia and dysarthria . This was replicated in our four patients who developed a generalized ataxia around the age of 3 to 4 years.…”

Clinical Reasoning: Progressive cognitive decline, cerebellar ataxia, recurrent myoclonus, and epilepsy

“…Kufs disease is the adult-onset form of NCL, which lacks the typical visual impairment seen in other subtypes. 4 Two different and often overlapping forms have been described: type A, which is characterized by myoclonic epilepsy, ataxia, and dysarthria; and type B, which is characterized by severe cognitive impairment. 5 Disease onset is usually in the third decade of life but onset in teenagers has also been reported.…”

“…5 Disease onset is usually in the third decade of life but onset in teenagers has also been reported. 3,4 Two gene mutations have been reported to account for the majority of patients: DNAJC5 mutations lead to the autosomal dominant inherited type Kufs disease and CLN6 mutations cause the autosomal recessive inherited type Kufs disease. 6 Cerebral MRI usually shows brain atrophy.…”

“…Mutations of CLN6 were identified in variant of lateinfantile NCL (vLNCL) and recessive Kufs disease type A. 3,4 Patients with vLNCL experience symptom onset at an age between 18 months and 5 years, with loss of vision. Since our patient did not show visual impairment as a teenager, we excluded vLNCL.…”

Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease)

“…Kufs type A presents with progressive myoclonus epilepsy, whereas Kufs type B presents with dementia and motor signs. 6,13 Recessive mutations in CLN6 [14][15][16] and dominant mutations in DNAJC5 [17][18][19] can cause Kufs type A; Kufs type B can be caused by recessive mutations in CTSF. 20,21 Rare cases of ANCL with retinal involvement are described due to mutations in PPT1 (CLN1), 22,23 CLN5, 24,25 and GRN.…”