Severe microcephalyGene: TCF4
Comment on list classification: Promoting this gene from grey to red. After consultation with the Genomics England Clinical Team it was decided that patients with Pitt-Hopkins syndrome are more likely to be following a route for explanation of global developmental delay/intellectual disability than severe microcephaly.
Created: 30 Jun 2021, 11:59 a.m. | Last Modified: 30 Jun 2021, 11:59 a.m.
Panel Version: 2.210
Microcephaly listed as a feature of Pitt-Hopkins syndrome #610954 (AD) in OMIM.
PMID:18728071 - Zweier et al 2008 - analysed TCF4 in 117 patients with a phenotype suggestive of Pitt-Hopkins syndrome. 16 were found to have TCF4 variants. All had severe mental retardation. Microcephaly was observed in 9/16 but the degree is not stated.
PMID: 21671391 - Marangi et al 2011 - report 14 Pitt-Hopkins syndrome patients with TCF4 mutations; 2 patients had large 18q21.2 chromosome deletions involving TCF4, 11 patients had gene mutations and one had a balanced translocation involving the TCF4 locus. 2 are reported with a OFC at or below the 3rd percentile at birth, and 7/14 with postnatal microcephaly but the degree is not stated.
PMID: 29318938 - Goodspeed et al 2018 - reviewed 25 case reports and case series of Pitt-Hopkins Syndrome published in the literature from 2007 to 2016, and found 282 cases reported in total. Microcephaly was noted in 85/144 (59%) cases, but the severity is not discussed.
PMID:22934316 - GeneReviews entry.
Created: 26 May 2021, 9:18 p.m. | Last Modified: 26 May 2021, 9:18 p.m.
Panel Version: 2.185
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pitt-Hopkins syndrome OMIM:610954
Well established gene-disease association. Microcephaly reported in around 60%.
Sources: Expert list
Created: 4 Sep 2020, 1:58 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pitt-Hopkins syndrome, MIM# 610954
Variants in this GENE are reported as part of current diagnostic practice
Gene: tcf4 has been classified as Red List (Low Evidence).
Phenotypes for gene: TCF4 were changed from Pitt-Hopkins syndrome, MIM# 610954 to Pitt-Hopkins syndrome, OMIM:610954
Publications for gene: TCF4 were set to 18728071; 22934316
gene: TCF4 was added gene: TCF4 was added to Severe microcephaly. Sources: Expert list Mode of inheritance for gene: TCF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TCF4 were set to 18728071; 22934316 Phenotypes for gene: TCF4 were set to Pitt-Hopkins syndrome, MIM# 610954 Review for gene: TCF4 was set to GREEN gene: TCF4 was marked as current diagnostic