Table 2.

Select Features of TRIO-Related Neurodevelopmental Disorder

FeatureProportion of Persons w/FeatureComment
TRIO-NDD due to GOF variant 1TRIO-NDD due to LOF variant 2
Neurodevelopment Developmental delay (DD) 20/2036/36Moderate-to-severe DD in most w/TRIO GOF variant; mild-to-moderate DD in those w/TRIO LOF variant
Intellectual disability ~20/20Common
Neurobehavioral manifestations 15/1829/31Stereotypies, poor attention, aggressive behavior, obsessive-compulsive findings, autistic findings
Seizures ~7/19~7/29Seizures may be more common than reported.
Macrocephaly 11/182/35
Microcephaly –25/35
Feeding / Growth / Gastrointestinal Infant feeding difficulties 12/1719/28
Poor weight gain / Early growth deficiency 8/108/11
Constipation 6/1612/26
Musculoskeletal Short &/or tapering fingers 6/1714/31
2-3 toe syndactyly –5/15
Scoliosis 7/164/27
Dysmorphic facial features CommonCommon
Dental abnormalities 5/1517/29
Cardiac anomalies 2/183/26

– = feature is not reported as part of this phenotype; GOF = gain-of-function; LOF = loss-of-function

1.

TRIO gain-of-function variants are missense variants within the spectrin repeat domain that lead to increased Rac1 activation (see Molecular Pathogenesis). Twenty individuals with gain-of-function TRIO variants are included in this table. The denominator indicates how many individuals were screened for the particular feature.

2.

TRIO loss-of-function variants include missense variants within the GEFD1 domain, truncating variants throughout the gene, and intragenic deletions that lead to loss of Rac1 activation (see Molecular Pathogenesis). Thirty-six individuals with loss-of-function TRIO variants are included in this table. The denominator indicates how many individuals were screened for the particular feature.

From: TRIO-Related Neurodevelopmental Disorder

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