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| Hereditary Spastic Paraplegia - paediatric v1.85 | INPP4A |
Chirag Patel gene: INPP4A was added gene: INPP4A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INPP4A were set to PMID: 39315527 Phenotypes for gene: INPP4A were set to INPP4A-related neurodevelopmental disorder Review for gene: INPP4A was set to GREEN Added comment: PMID: 39315527 30 individuals (aged 6 months to 40 years) from 17 unrelated families with biallelic LOF variants in INPP4A gene (11 nonsense or frameshift and 3 missense, mostly exon 4). Cardinal clinical features include: severe global developmental delay, profound speech impairment, severe-profound intellectual disability, and severe lower limb weakness/paralysis. More variable clinical features include: microcephaly, short stature, cerebellar signs, involuntary movements, axial hypotonia, spasticity, quadriparesis, joint contractures, seizures, visual impairment. Neuroimaging findings vary from normal to features of (ponto)cerebellar hypoplasia, ventriculomegaly, reduced cerebral volume and hypomyelination. A more severe presentation is seen with variants downstream of exon 4. Preliminary fibroblast cell studies identify disruption of endocytic pathways as the likely mechanism of disease, consistent with previous findings of a role of INPP4A in endocytosis. All mouse models display a phenotype mirroring human INPP4A-related neurodevelopmental disorder entailing a severe movement disorder with inability to walk, a small brain, and poor growth/weight gain. Sources: Literature |
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| Hereditary Spastic Paraplegia - paediatric v1.1 | DDHD2 |
Zornitza Stark changed review comment from: At least 7 families reported. Affected individuals have delayed development, intellectual disability, and early-onset spasticity of the lower limbs. Brain MRI shows a thin corpus callosum and periventricular white matter lesions. Brain magnetic resonance spectroscopy shows an abnormal lipid peak. Sources: Expert list; to: More than 10 families reported. Affected individuals have delayed development, intellectual disability, and early-onset spasticity of the lower limbs. Brain MRI shows a thin corpus callosum and periventricular white matter lesions. Brain magnetic resonance spectroscopy shows an abnormal lipid peak. Sources: Expert list |
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| Hereditary Spastic Paraplegia - paediatric v0.155 | MAG | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.155 | MAG | Zornitza Stark changed review comment from: Spastic paraplegia-75 is an autosomal recessive, slowly progressive neurodegenerative disorder characterized by onset of spastic paraplegia and cognitive impairment in childhood. Eight unrelated families reported.; to: Spastic paraplegia-75 is an autosomal recessive, slowly progressive neurodegenerative disorder characterized by onset of spastic paraplegia and cognitive impairment in childhood. Eight unrelated families reported with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.155 | MAG | Zornitza Stark Phenotypes for gene: MAG were changed from Spastic paraplegia 75, autosomal recessive, 616680 to Spastic paraplegia 75, autosomal recessive, 616680; Cerebellar ataxia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.154 | MAG | Zornitza Stark edited their review of gene: MAG: Changed phenotypes: Spastic paraplegia 75, autosomal recessive, MIM# 616680, Cerebellar ataxia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.154 | MAG | Zornitza Stark edited their review of gene: MAG: Added comment: Four more individuals reported with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms.; Changed publications: 24482476, 26179919, 31402626, 32629324, 32629324 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.128 | MAG | Zornitza Stark Marked gene: MAG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.128 | MAG | Zornitza Stark Gene: mag has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.128 | MAG | Zornitza Stark Publications for gene: MAG were set to 31402626; 24482476; 26179919 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.127 | MAG | Zornitza Stark reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 26179919, 31402626, 32629324; Phenotypes: Spastic paraplegia 75, autosomal recessive, MIM# 616680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.34 | KIF1A |
Zornitza Stark gene: KIF1A was added gene: KIF1A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list Mode of inheritance for gene: KIF1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: KIF1A were set to 26410750; 21487076; 22258533; 32096284; 31488895; 29159194; 25585697 Phenotypes for gene: KIF1A were set to Spastic paraplegia 30, MIM# 610357 Review for gene: KIF1A was set to GREEN Added comment: Spastic paraplegia-30 (SPG30) is a neurologic disorder characterized by onset of slowly progressive spastic paraplegia in the first or second decades of life. Affected individuals have unsteady spastic gait and hyperreflexia of the lower limbs. Some patients have a 'pure' form of the disorder, limited to spastic paraplegia, whereas others may have a 'complicated' form that includes cognitive dysfunction, learning disabilities, or behavioral abnormalities, peripheral sensorimotor neuropathy, urinary sphincter problems, and/or cerebellar atrophy with thin corpus callosum on brain imaging. The phenotypic features represent a spectrum of abnormalities of the central, peripheral, and autonomic nervous system. Mono-allelic and bi-allelic variants can both cause HSP, multiple families reported with both. Sources: Expert list |
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| Hereditary Spastic Paraplegia - paediatric v0.28 | GBA2 |
Zornitza Stark gene: GBA2 was added gene: GBA2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list Mode of inheritance for gene: GBA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GBA2 were set to 23332916; 23332917 Phenotypes for gene: GBA2 were set to Spastic paraplegia 46, autosomal recessive, MIM# 614409 Review for gene: GBA2 was set to GREEN Added comment: A neurodegenerative disorder characterized by onset in childhood of slowly progressive spastic paraplegia and cerebellar signs. Some patients have cognitive impairment, cataracts, and cerebral, cerebellar, and corpus callosum atrophy on brain imaging. Sources: Expert list |
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| Hereditary Spastic Paraplegia - paediatric v0.26 | FA2H |
Zornitza Stark gene: FA2H was added gene: FA2H was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FA2H were set to 20104589; 23745665; 19068277; 20853438; 22146942 Phenotypes for gene: FA2H were set to Spastic paraplegia 35, autosomal recessive, MIM# 612319 Review for gene: FA2H was set to GREEN Added comment: Complex form of HSP characterized by childhood onset of gait difficulties due to progressive spastic paraparesis, dysarthria, and mild cognitive decline associated with leukodystrophy on brain imaging. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur. In addition, some indviduals have radiographic evidence of neurodegeneration with brain iron accumulation (NBIA). Sources: Expert list |
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| Hereditary Spastic Paraplegia - paediatric v0.19 | DDHD2 |
Zornitza Stark gene: DDHD2 was added gene: DDHD2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list Mode of inheritance for gene: DDHD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DDHD2 were set to 23486545; 24482476; 23176823 Phenotypes for gene: DDHD2 were set to Spastic paraplegia 54, autosomal recessive, MIM# 615033 Review for gene: DDHD2 was set to GREEN Added comment: At least 7 families reported. Affected individuals have delayed development, intellectual disability, and early-onset spasticity of the lower limbs. Brain MRI shows a thin corpus callosum and periventricular white matter lesions. Brain magnetic resonance spectroscopy shows an abnormal lipid peak. Sources: Expert list |
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| Hereditary Spastic Paraplegia - paediatric v0.0 | MAG |
Bryony Thompson gene: MAG was added gene: MAG was added to Hereditary Spastic Paraplegia - paediatric_RMH. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAG were set to 31402626; 24482476; 26179919 Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, 616680 |
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