Craniofacial Phenotypes and Genetics of DiGeorge Syndrome

Abstract

The 22q11.2 deletion is one of the most common genetic microdeletions, affecting approximately 1 in 4000 live births in humans. A 1.5 to 2.5 Mb hemizygous deletion of chromosome 22q11.2 causes DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). DGS/VCFS are associated with prevalent cardiac malformations, thymic and parathyroid hypoplasia, and craniofacial defects. Patients with DGS/VCFS manifest craniofacial anomalies involving the cranium, cranial base, jaws, pharyngeal muscles, ear-nose-throat, palate, teeth, and cervical spine. Most craniofacial phenotypes of DGS/VCFS are caused by proximal 1.5 Mb microdeletions, resulting in a hemizygosity of coding genes, microRNAs, and long noncoding RNAs. TBX1, located on chromosome 22q11.21, encodes a T-box transcription factor and is a candidate gene for DGS/VCFS. TBX1 regulates the fate of progenitor cells in the cranial and pharyngeal apparatus during embryogenesis. Tbx1-null mice exhibit the most clinical features of DGS/VCFS, including craniofacial phenotypes. Despite the frequency of DGS/VCFS, there has been a limited review of the craniofacial phenotypes of DGC/VCFS. This review focuses on these phenotypes and summarizes the current understanding of the genetic factors that impact DGS/VCFS-related phenotypes. We also review DGS/VCFS mouse models that have been designed to better understand the pathogenic processes of DGS/VCFS.

Síndrome de DiGeorge (deleção do cromossomo 22q11.2): manejo e prognóstico

“…Brazilian Journal of Development, Curitiba, v.9, n.1, p. 3995-4012, jan., 2023 Ademais, as manifestações clínicas não se limitam apenas à tríade, como também a outras anomalias congênitas, como distúrbios da formação do palato e face, gastrointestinais e renais, imunológicos, atraso cognitivo e doenças psiquiátricas ((FUNATO, 2022;CIRILLO et al, 2022;BERNSTOCK et al, 2020).…”

“…A SDG, por ter um quadro clínico é baseado em uma expressão variável de fenótipos que variam de formas leves a graves e com risco de vida, tendo em vista o acometimento multissistêmico, por vezes possui seu diagnóstico atrasado. Ademais, a falta de reconhecimento a respeito dos testes genéticos também o retarda (FUNATO, 2022;CIRILLO et al, 2022;BERNSTOCK et al, 2020;GARKABY et al, 2022).…”

Deletion Syndrome 22q11.2: A Systematic Review

“…Variability in gene expression causes differences between patients at the phenotypic level. Craniofacial anomalies and alterations in the development of the thymus and heart stand out [ 3 , 4 , 5 ].…”

<strong>Analysis of <em> FOXE1</em> rs4460498 and <em> GSTP-1 I105V </em> associated with non syndromic cleft lip and palate among Deutero Malay Subrace in Indonesia</strong>

“…NS CLP disorder occurs more in the Asian population than in the African population. 7,8 Syndromic CLP (S CLP) is usually associated with the presence of other malformations or syndromes such as Stickler's syndrome, Van der Woude's syndrome and DiGeorge syndrome while NS CLP is not associated with other disorders, 9,10,11 and the cases are due to monogenic or Mendelian disorder. 12 The prevalence rate of NS CLP is estimated at 76.8% of a total of 5,918 cases of CLP, and 7.3% of cases were S CLP, this results may vary based on geographic area, ethnicity, and socioeconomic status.…”