Table 5 Medical and neurological disorders with known or suspected maternal inheritance
From: Maternal transmission of Alzheimer's disease: Prodromal metabolic phenotype and the search for genes
Disorder | Mechanism | Clinical phenotype | Reference |
|---|---|---|---|
Kearns-Sayre syndrome | mtDNA deletions present at levels up to 80% of total mtDNA. The most frequent is 4977 bp deletion | Paralysis of the extraocular muscles, pigmentary retinopathy, heart block, cerebellar ataxia and elevated CSF proteins | Maceluch et al. [157] |
Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) | mtDNA mutation: A3243G (tRNALeu(UUR)) | Children and young adults. Recurrent vomiting, migraine-like headache, stroke-like episodes causing cortical blindness, hemiparesis or hemianopia | Thambisetty et al. [158] |
Myoclonic epilepsy with ragged red fibres (MERRF) | mtDNA mutation: A8344G, T8356C, G8363A (tRNALys) | Myclonus, seizures, mitochondrial myopathy and cerebellar ataxia; less common signs can include dementia, hearing loss, peripheral neuropathy and multiple lipomas | DiMauro et al. [159] |
Neuropathy, ataxia, retinitis pigmentosa (NARP) | mtDNA mutation: T8993G, T8993C (nt-8993 at the ATPase6 gene) | Retinitis pigmentosa, dementia, seizures, ataxia, proximal weakness and sensory neuropathy | Holt et al. [160] |
Maternally inherited Leigh syndrome (MILS) | mtDNA mutation: T8993G, T8993C (nt-8993 at the ATPase6 gene) | Symmetrical lesions in the basal ganglia and the brainstem | Holt et al. [160] |
Leber's hereditary optic neuropathy (LHON) | mtDNA mutation: G11778A (ND4 gene), G3460A (ND1 gene), T14484C (ND6 gene) | Acute or subacute loss of vision in young adults due to bilaterally optic neuropathy | Yen et al. [161] |
Progressive external ophthalmoplegia (PEO) | mtDNA mutation in genes encoding tRNALeu, tRNAIle and tRNAAsn | Progressive paralysis of the extraocular muscles | Silvestri et al. [162] |
Maternally inherited diabetes and deafness (MIDD) | mtDNA mutation: A3243G (tRNALeu) | Impaired glucose tolerance (IGT)/diabetes, sensorineural deafness. Other symptoms are: macular pattern dystrophy (86%), myopathy (43%), cardiomyopathy (15%), neurological abnormalities and neuropsychiatric symptoms (18%), gastrointestinal and renal dysfunction | Hosszufalusi et al. [163] |
Juvenile myoclonic epilepsy | Genomic imprinting: EJM-1 (chromosome 6) | Seizures | Pal et al. [164] |
Tourette's syndrome | Genomic imprinting | Multiple physical (motor) and vocal (phonic) tics | Eapen et al. [165] |
Angelman syndrome | Genomic imprinting (chromosome 15) | Intellectual and developmental delay, sleep disturbance, seizures, jerky movements, frequent laughter or smiling and usually a happy demeanour | Horsthemke et al. [166] |
Autism | Genomic imprinting (chromosome 15) | Autism | Cook et al. [167] |
Fragile X syndrome | Unstable expansions of a CGG trinucleotide repeat located in the first exon (non-protein-coding) of the FMR1 gene (for fragile X mental retardation) | Stereotypic movements and atypical social development up to autism. Cluttered or nervous speech; intellectual disability (from mild to severe); elongated face, large or protruding ears, flat feet and low muscle tone | Mandel et al. [132] |
Friedreich ataxia | GAA repeat expansion (chromosome 9) | Ataxia, gait disturbance, speech problems, heart disease (in some cases) | La Pean et al. [133] |
Myotonic dystrophy | CTG repeat expansion | Muscle weakness, cataract, myotonia, infertility | Botta et al. [134] |