IllnessAmyotrophic lateral sclerosis [rarely mutated genes], differential diagnosis

NGS +

Amyotrophic lateral sclerosis (ALS) is a progressive disease affecting motor neurons in the spinal cord and brain, the atrophy of which results in muscle weakness, loss of muscle mass and inability to control movement. Different ALS forms can be distinguished based on symptomatology and genetics. >90% of cases occur sporadically with initial signs in the late fifties or later. 5-10% of patients have a family history of ALS or with related disorders, e.g. frontotemporal dementia (FTD). Familial ALS typically begins in the late forties or fifties; juvenile ALS is rare. Most ALS patients die within 2-10 years after the onset mostly of respiratory failure symptoms. The course of the disease can vary widely. One-fifth of ALS patients also develop FTD with changes in personality, behavior and communication skills. A rare, often familial form of ALS is known as ALS-Parkinsonism-Dementia complex. Most forms of ALS are inherited in an autosomal dominant manner - with incomplete penetrance. Less commonly, ALS is inherited autosomal recessively and very rarely in an X-linked dominant manner. Mutations in the C9orf72 gene are responsible for at least one-third of familial ALS in Western countries. Worldwide, mutations in the SOD1 gene cause 15-20% of familial ALS, and mutations in the TARDBP and FUS genes each account for about 5% of cases. The other ALS genes each cause only a small proportion of the cases. Mutations can be confirmed in about 60% of cases with familial ALS. Therefore, a negative molecular genetic result by no means excludes the clinical diagnosis.

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

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

• Alias: Amyotrophic lateral sclerosis, ALS
• Alias: Charcot disease
• Alias: Familial amyotrophic lateral sclerosis
• Alias: Lou Gehrig disease
• Allelic: Charcot-Marie-Tooth disease, type 2Y (VCP)
• Allelic: Charcot-Marie-Tooth disease, type 4J (FIG4)
• Allelic: Dementia, familial, nonspecific (CHMP2B)
• Allelic: Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8 (TBK1)
• Allelic: Glaucoma 1, open angle, E (OPTN)
• Allelic: Glaucoma, normal tension, susceptibility to (OPTN)
• Allelic: Inclusion body myopathy early Paget disease + frontotemporal dementia 1 (VCP)
• Allelic: Inclusion body myopathy wtih early-onset Paget disease without frontotemporal (HNRNPA1)
• Allelic: Inclusion body myopathy, early Paget disease, no frontotemporal dementia 3 (HNRNPA1)
• Allelic: Myopathy, isolated mitochondrial, AD (CHCHD10)
• Allelic: Neuronopathy, distal hereditary motor, type VIIB (DCTN1)
• Allelic: Perry syndrome [parkinsonism, depression, weight loss + hypoventilation] (DCTN1)
• Allelic: Polymicrogyria, bilateral temporooccipital (FIG4)
• Allelic: Short-rib thoracic dysplasia 6 with/-out polydactyly (NEK1)
• Allelic: Spastic paralysis, infantile onset ascending (ALS2)
• Allelic: Spinal muscular atrophy, Jokela type (CHCHD10)
• Allelic: Spinal muscular atrophy, late-onset, Finkel type (VAPB)
• Allelic: Spinocerebellar ataxia, AR, with axonal neuropathy 2 (SETX)
• Allelic: Yunis-Varon syndrome [cleidocranial dysplasia, digital anomalies, neuron loss] (FIG4)
• Amyotrophic lateral sclerosis 11 (FIG4)
• Amyotrophic lateral sclerosis 12 (OPTN)
• Amyotrophic lateral sclerosis 14, with/-out frontotemporal dementia (VCP)
• Amyotrophic lateral sclerosis 15, with/-out frontotemporal dementia (UBQLN2)
• Amyotrophic lateral sclerosis 17 (CHMP2B)
• Amyotrophic lateral sclerosis 18 (PFN1)
• Amyotrophic lateral sclerosis 19 (ERBB4)
• Amyotrophic lateral sclerosis 2, juvenile (ALS2)
• Amyotrophic lateral sclerosis 20 (HNRNPA1)
• Amyotrophic lateral sclerosis 21 (MATR3)
• Amyotrophic lateral sclerosis 22 with/-out frontotemporal dementia (TUBA4A)
• Amyotrophic lateral sclerosis 23 (ANXA11)
• Amyotrophic lateral sclerosis 4, juvenile (SETX)
• Amyotrophic lateral sclerosis 8 (VAPB)
• Amyotrophic lateral sclerosis 9 (ANG)
• Amyotrophic lateral sclerosis, susceptibility to (ALS2)
• Amyotrophic lateral sclerosis, susceptibility to (DCTN1)
• Amyotrophic lateral sclerosis, susceptibility to, 24 (NEK1)
• Fazio-Londe disease [bulbar palsy]; Brown-Vialetto-Van Laere syndrome 1 (SLC52A3)
• Fazio-Londe disease [bulbar palsy]; Brown-Vialetto-Van Laere syndrome 2 (SLC52A2)
• Fronto-temporal dementia (TBK1)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (CHCHD10)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (TBK1)
• Primary lateral sclerosis, juvenile (ALS2)