IllnessDemenz, Manifestation<60 Jahre oder familiäre Häufung

NHS + X

[Sanger]

In contrast to late-onset Alzheimer disease (AD), there are only a few families with early-onset dementia, usually inherited in an autosomal dominant manner and often caused by mutations in a gene with high penetrance. In addition to early onset AD, frontotemporal and other familial dementias can also be defined by molecular genetics. The genetic basis of AD is best understood in these early-onset forms, but they account for <1% of cases being inherited in an autosomal dominant manner. Frontotemporal dementia is the second most common cause of dementia, about 20-50% of cases are familial, with mutations in three genes found in 60% of familial cases, of which C9orf72 mutations are the most common (25%) and <5% of mutations occur in other genes. Less than 2% of patients with early dementia harbor presenilin 1/2 or amyloid precursor protein mutations as triggers. The German guidelines specify eight core genes, >20 additional genes cover the entire causative mutation spectrum even with respect to very rare forms. DNA-diagnostic yields for monogenic dementias hardly reach more than one third in cases of high familiality. The clinical diagnosis can by no means be excluded by a negative molecular genetic result.

References: https://www.ncbi.nlm.nih.gov/books/NBK268647/

https://www.ncbi.nlm.nih.gov/books/NBK1476/

https://www.ncbi.nlm.nih.gov/books/NBK304142/

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

https://www.ncbi.nlm.nih.gov/books/NBK1224/

https://www.ncbi.nlm.nih.gov/books/NBK1450/

https://www.ncbi.nlm.nih.gov/books/NBK1197/

https://www.ncbi.nlm.nih.gov/books/NBK1438/

https://www.ncbi.nlm.nih.gov/books/NBK1491/

https://www.ncbi.nlm.nih.gov/books/NBK84112/

• Alias: Alzheimer disease
• Alias: Frontotemporale Demenz
• Alias: Parkinson-Demenz
• Alias: Pick-Demenz
• Alias: Vaskuläre Demenz
• Allelic: Acne inversa, familial, 3 (PSEN1)
• Allelic: Amyotrophic lateral sclerosis 17 (CHMP2B)
• Allelic: Amyotrophic lateral sclerosis, susceptibility to, 13 (ATXN2)
• Allelic: Aphasia, primary progressive (GRN)
• Allelic: Cardiomyopathy, dilated, 1U (PSEN1)
• Allelic: Cardiomyopathy, dilated, 1V (PSEN2)
• Allelic: Ceroid lipofuscinosis, neuronal, 11(GRN)
• Allelic: Charcot-Marie-Tooth disease, type 2Y (VCP)
• Allelic: Dementia, frontotemporal (PSEN1)
• Allelic: Inclusion body myopathy, early-onset Paget disease + frontotemporal dementia 1 (VCP)
• Allelic: Myopathy, isolated mitochondrial, AD (CHCHD10)
• Allelic: Neuropathy, hereditary sensory, type IE (DNMT1)
• Allelic: Parkinson disease, late-onset, susceptibility to (ATXN2)
• Allelic: Parkinson disease, susceptibility to (TBP)
• Allelic: Retinal dystrophy with inner retinal dysfunction + ganglion cell abnormalities (ITM2B)
• Allelic: Spinal muscular atrophy, Jokela type (CHCHD10)
• Allelic: Supranuclear palsy, progressive (MAPT)
• Allelic: Supranuclear palsy, progressive atypical (MAPT)
• Alzheimer disease 3 (PSEN1)
• Alzheimer disease 4 (PSEN2)
• Alzheimer disease, type 3, with spastic paraparesis + apraxia (PSEN1)
• Alzheimer disease, type 3, with spastic paraparesis + unusual plaques (PSEN1)
• Amyotrophic lateral sclerosis 14, with/-out frontotemporal dementia (VCP)
• Amyotrophic lateral sclerosis 15, with/-out frontotemporal dementia (UBQLN2)
• Brain abnormalities, neurodegeneration + dysosteosclerosis (CSF1R)
• Cerebellar ataxia, deafness, narcolepsy, AD (DNMT1)
• Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants (APP)
• Ceroid lipofuscinosis, neuronal, 4, Parry type (DNAJC5)
• Congenital hypotonia, epilepsy, developmental delay, digital anomalies (ATN1)
• Dementia, familial British (ITM2B)
• Dementia, familial Danish (ITM2B)
• Dementia, frontotemporal, with/-out parkinsonism (MAPT)
• Dentatorubral-pallidoluysian atrophy (ATN1_CAG)
• Epilepsy, progressive myoclonic 2A [Lafora] (EPM2A)
• Epilepsy, progressive myoclonic 2B [Lafora] (NHLRC1)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (C9ORF72_GGGGCC)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (CHCHD10)
• Frontotemporal lobar degeneration with ubiquitin-positive inclusions (GRN)
• Huntington disease-like 2 (JPH3_CTG)
• Leukoencephalopathy, diffuse hereditary, with spheroids (CSF1R)
• McLeod neuroacanthocytosis syndrome [MONDO:0018945, panelapp] (XK)
• McLeod syndrome +/- chronic granulomatous disease (XK)
• Pick disease (MAPT, PSEN1)
• Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (TYROBP)
• Spinocerebellar ataxia 1 (ATXN1_CAG)
• Spinocerebellar ataxia 1 (ATXN1_CAG)Spinocerebellar ataxia 17 (TBP_CAG)
• Spinocerebellar ataxia 2 (ATXN2_CAG)