IllnessCeroid-Lipofuscinosis, neuronal; differential diagnosis

NGS +

Neuronal ceroid lipofuscinoses are a group of clinically and genetically heterogeneous hereditary degenerative neurologic disorders that share the neuropathologic features of neuronal cell loss, particularly in the cerebral and cerebellar cortex, and accumulation of lipofuscin with characteristic ultrastructural appearance. Myoclonic and other seizure types occur. Developmental delays, dementia, and visual disturbances (especially in childhood forms) are variously associated with specific neuronal ceroid lipofuscinosis syndromes. There are more than a dozen forms of these neuronal ceroid lipofuscinoses, which are classified according to age at symptom onset or causative gene mutations. Most of the neuronal ceroid lipofuscinoses are inherited in an autosomal recessive manner, and less commonly in an autosomal dominant manner. Using Sanger sequencing, the diagnostic yield has been reported to be close to 30%. Thus, a negative result does not represent exclusion of the diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1371/

https://doi.org/10.1186/s13024-018-0300-6

• Alias for all fuscinoses: Batten disease (CLN3)
• Alias: Jansky–Bielschowsky disease (CLN2)
• Alias: Spielmeyer-Sjogren disease (CLN3)
• Alias: Vogt-Spielmeyer disease (CLN3)
• Aphasia, primary progressive; Dementia hereditary dysphasic disinhibition (GRN)
• CLN2, variable age of onset; Jansky-Bielschowsky disease (TPP1)
• CLN5: NCL, late infantile, Finnish variant; Finnish vLINCL (CLN5)
• Ceroid lipofuscinosis, neuronal, 1, variable age of onset (PPT1)
• Ceroid lipofuscinosis, neuronal, 10; CLN, cathepsin D-deficient; CLN, congenital (CTSD)
• Ceroid lipofuscinosis, neuronal, 11 (GRN)
• Ceroid lipofuscinosis, neuronal, 13, Kufs type (CTSF)
• Ceroid lipofuscinosis, neuronal, 14 (KCTD7)
• Ceroid lipofuscinosis, neuronal, 2; Spinocerebellar ataxia, AR 7 (TPP1)
• Ceroid lipofuscinosis, neuronal, 3
• Ceroid lipofuscinosis, neuronal, 4, Parry type; Kufs disease, AD (DNAJC5)
• Ceroid lipofuscinosis, neuronal, 5 (CLN5)
• Ceroid lipofuscinosis, neuronal, 6; CLN, Kufs type, adult onset (CLN6)
• Ceroid lipofuscinosis, neuronal, 7; Macular dystrophy with central cone involvement (MFSD8)
• Ceroid lipofuscinosis, neuronal, 8; CLN, 8, Northern epilepsy variant (CLN8)
• DD: Epilepsy, progressive myoclonic 1A [Unverricht + Lundborg] (CSTB)
• DD: Epilepsy, progressive myoclonic 2A [Lafora] (NHLRC1)
• DD: Epilepsy, progressive myoclonic 2B [Lafora] (NHLRC1)
• Dent disease; Hypophosphatemic rickets; Nephrolithiasis, type I (CLCN5)
• Epilepsy, progressive myoclonic 3, with/-out intracellular inclusions (KCTD7)
• Frontotemporal lobar degeneration with ubiquitin-positive inclusions (GRN)
• Kufor-Rakeb syndrome; Spastic paraplegia 78, AR (ATP13A2)
• Neuronal ceroid lipofuscinosis, NCL, infantile
• Neuronal ceroid lipofuscinosis, juvenile; JNCL (CLN3)
• Parkinson disease 9, Ar, juvenile-onset; PARK9 (ATP13A2)
• Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis (CLCN5)
• Santavuori disease; Sanatvuori-Haltia disease; CLN1 (PPT1)