Genetic Basis of Short Face Syndrome in Eastern Mediterranean Families

Abstract

Introduction: The short face syndrome reflects a vertical dimension dysmorphology characterized by decreased lower face height, hypodivergent growth pattern, flat mandibular plane, and closed gonial angle. Contributing factors include skeletal dysmorphology and hyperfunction of the masticatory muscles.

Aim: To investigate the inheritance pattern and the genes involved in the short face syndrome, explore the genes involved in this vertical dysplasia., and analyze the correlation between this vertical dysplasia and the different sagittal malocclusions.

Methods: The sample consists of subjects from 2 families diagnosed with short face syndrome through lateral cephalometric radiographs taken routinely to assess skeletal and dentoalveolar features and corresponding clinical. Upon IRB approval, family members affected and non-affected with the condition consented to have 5cc of blood drawn for genetic testing. Next Generation Sequencing (NGS) was used and a Whole Exome sequencing (WES) was applied to gauge the genetic determinants of the short face syndrome.

Results: A Mendelian inheritance pattern was observed segregating in either an autosomal dominant, X-linked manner in family A and autosomal recessive in family B. Pedigree analysis showed equally affected males and females. Extraoral photographs demonstrated that SFS is transmitted with different levels of penetrance. Cephalometric analysis on affected subjects revealed a decreased lower facial height, a hypodivergent facial pattern, and a tendency towards a skeletal class II. Genetic analysis denoted the presence of 4 novel genes affecting skeletal development.

Conclusion: This is the first study evaluating the inheritance pattern and genetic contribution to SFS. It illustrated the clinical, cephalometric characteristics of affected individuals and shed light on the genetic map responsible for the development of SFS. It is the first study to evaluate hypodivergence independently of class II,2.