Table 2.

GNAO1-Related Disorder: Genotype-Phenotype Correlations

Variant# of PersonsClinical Characteristics
EpilepsyMovement disorder (predominantly dystonia & chorea) 1DD/ID 2
p.Gly40Arg 38All had DEENot a prominent featureProfound global DD/ID
p.Gly40Trp 42
p.Gly40Glu 52
p.Gly203Arg 625All had DEEPresent in most to all; hyperkinetic crises commonSevere global DD/ID in 2; not stated in 9
p.Arg206Gln 74 (from 1 family)No seizuresDystonia (onset at ages 15 yrs, 30 yrs, & 47 yrs, + 1 asymptomatic at 30 yrs); no chorea or hyperkinetic crises reportedNo speech delay; motor delay NR; no ID
p.Arg209Cys 819Seizures mostly focal or generalized tonic-clonic; none had DEEPresent in most to all; hyperkinetic crises commonModerate-to-severe global DD; mild-to-severe ID
p.Arg209His 913Seizures rarePresent in all; hyperkinetic crises commonModerate-to-severe global DD; ID not stated
p.Arg209Leu 103
p.Arg209Gly 111
p.Arg209Pro 121
p.Cys215Tyr 134 (from 3 families)No seizuresDystonia onset at age 3-6 yrs; no chorea; hyperkinetic crises in 1/4.No speech delay; motor delay NR; mild ID in 3/4; no ID in 1/4 (person w/affected child)
p.Glu237Lys 1418No seizuresPresent in all; hyperkinetic crises commonModerate-to-severe global DD; normal IQ for 1/10; not stated for 9/10
p.Glu246Lys 1518Seizures in 2/18 (not DEE)Present in most or all; hyperkinetic crises commonSevere global DD; ID varies (severe to profound); two persons assessed w/eye-tracking system had "normal fluid intelligence & lexical comprehension" 16
c.724-8A>G 1721 (from 18 families)No seizures 18Present in all; hyperkinetic crises uncommon (observed in 1 person)DD in 1st yr of life; most (not all) had ID, often mild

DD = developmental delay; DEE = developmental and epileptic encephalopathy; ID = intellectual disability; NR = not reported

1.

Movement disorders are typically not the presenting manifestation. More often, initial presenting manifestations are seizures and/or hypotonia and developmental delay.

2.

Not all reports provide this information. Of those that do, many do not distinguish between DD and ID.

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One of three affected family members reported by Vasconcellos et al [2023] had epilepsy; however, there was a family history of epilepsy in a deceased grandfather, who had no other reported manifestations of GNAO1-related disorder.

From: GNAO1-Related Disorder

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