Table 2.

Genotype-Phenotype Relationships of X-Linked Conditions in Humans

X-Linked Condition	Genotype	Sex Bias	Cognitive Symptoms	Evidence From Brain Organoids
Rett Syndrome	Heterozygous mutations in MECP2	Males die before birth or early infancy	Autism, epilepsy (148)	Altered interneuron populations in MECP2 mutant, with more VIP+ and CALB2+ cells in the mutant Increase in density of excitatory puncta in the mutant Recurring epileptiform-appearing spikes and high-frequency oscillations (120)
FXS	Heterozygous mutations in FMR1 gene	Females show milder symptoms	Intellectual disability, autism (149)	Accelerated neural progenitor cell cycle exit in FXS Reduced neural progenitor cell proliferation Number of GABAergic neurons decreased in FXS Accelerated synapse formation and hyperexcitability of synapses (121)
Klinefelter Syndrome	Males with extra X chromosome	Only affects males	Reading disabilities, autism (113,150)	Cellular phenotypes unknown. No evidence from brain organoids.
Turner Syndrome	Females missing part or all of 1 X chromosome	Only affects females	Intellectual disability, visual-spatial and cognitive weaknesses, autism (151,152)	Cellular phenotypes unknown. No evidence from brain organoids.

FXS, fragile X syndrome.