Table 1 |.

Neurogenetic conditions with developmental and degenerative phases

genetic alteration	Condition	Neurodevelopmental phenotype	Developmental brain pathology	Degenerative phenotype	Degenerative brain pathology
Trisomy 21	Down syndrome	Autism, intellectual disability	Small cerebrum, small cerebellum, dendritic spine abnormalities	Alzheimer disease	Alzheimer disease neuropathological changes
FMR1 full mutation (>200 repeats)	Fragile X syndrome	Autism, intellectual disability, attention deficit hyperactivity disorder	Heterotopias, enlarged caudate nucleus, dendritic spine abnormalities	Parkinsonism, ataxia	Largely unknown
FMR1 pre-mutation (55–200 repeats)	Fragile X-associated tremor/ataxia syndrome	Autism, anxiety, attention deficit hyperactivity disorder in a subset	–	Ataxia, intention tremor, parkinsonism	White matter degeneration, Purkinje cell loss, eosinophilic inclusions within neurons and glia
22q11.2 deletion	Velocardiofacial syndrome	Learning disabilities, intellectual disability, schizophrenia	Variable: polymicrogyria, heterotopias, developmental microvasculopathy	Early-onset parkinsonism	Nigral degeneration with Lewy body formation
c.598G>A mutation in PPP2R5D	NA	Intellectual disability	Macrocephaly	Early-onset parkinsonism	Nigral degeneration in the absence of Lewy body pathology
NR4A2 variants	NA	Intellectual disability	–	Early-onset parkinsonism	Yet to be studied post-mortem
RAB39B variants	NA	Intellectual disability	–	Early-onset parkinsonism	Nigral degeneration with Lewy body formation
H3F3A and H3F3B variants	NA	Intellectual disability	Yet to be studied post-mortem	Global neurodegeneration	Yet to be studied post-mortem
KIF1A variants	KIF1A-associated neurological disorder	Intellectual disability, seizures, spastic paraplegia	Microcephaly	Optic nerve atrophy, cerebral and cerebellar atrophy	Cerebellar atrophy, dentate nucleus and inferior olivary neuronal loss
HTT expansions	Huntington disease	Reduced brain growth compared with control individuals, epilepsy in ~25% individuals with juvenile-onset Huntington disease (age of onset <20 years)	Brain malformations in a subset, usually single unilateral heterotopias	Psychiatric disease, cognitive decline, chorea	Striatal degeneration, diffuse brain atrophy, formation of huntingtin aggregates

NA, not applicable.