Genetic Epilepsy

Gene: SATB1

Green List (high evidence)

Kohlschutter-Tonz syndrome-like (KTZSL) is characterized by global developmental delay with moderately to severely impaired intellectual development, poor or absent speech, and delayed motor skills. Although the severity of the disorder varies, many patients are nonverbal and have hypotonia with inability to sit or walk. Early-onset epilepsy is common and may be refractory to treatment, leading to epileptic encephalopathy and further interruption of developmental progress. Most patients have feeding difficulties with poor overall growth and dysmorphic facial features, as well as significant dental anomalies resembling amelogenesis imperfecta. This phenotype was reported in 28 patients (patients 13 to 40, PMID 33513338), including 9 patients from 3 families. Most variants were de novo, though some were inherited, suggestive of incomplete penetrance and variable expressivity.

Note Developmental delay with dysmorphic facies and dental anomalies, MIM# 619228 is a milder, allelic disorder.

Created: 21 Mar 2021, 7:10 a.m. | Last Modified: 21 Mar 2021, 7:10 a.m.

Panel Version: 0.1043

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Kohlschutter-Tonz syndrome-like, MIM# 619229

Green List (high evidence)

PMID: 33513338: 42 patients with SNVs. 28 de novo, 3 inherited from an affected parent.
Missense variants - more severe, profound ID
NMD PTCs - milder disease

Functional studies show missense variants have a STRONGER binding to downstream targets
Sources: Literature

Created: 1 Feb 2021, 5:02 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Neurodevelopmental disorders

Publications

• PMID: 33513338
• 33057194

Mode of pathogenicity
Other

I don't know

PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 12 de novo (2 frameshift, 7 missense, 1 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature

Created: 3 Nov 2020, 12:25 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental disorders

Publications

• 33057194