Cephalometric Evaluation of Children with Short Stature of Genetic Etiology: A Review

Abstract

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of the quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological centre of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the keywords: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and "Turner syndrome"; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its aetiology. The angular and linear cephalometric measurements differ from the measurements of the average normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusions: The greater part of the existing literature regarding cephalometric measurements in short-statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature should be the focus of future studies. These quantitative data are required to potentially establish cut-off values for reference for genetic testing based on craniofacial phenotypes.

Keywords: cartilage extracellular matrix; cephalometric radiograph; craniofacial morphology; epiphyseal growth plate; genetic syndromes; genetics; growth hormone/insulin-like growth factor 1 axis; short stature.

Figure 1

Factors affecting homeostasis of the epiphyseal growth plate and phenotypic manifestations of stature types resulting from complex interactions among these factors.

Figure 2

(A) Lateral cephalometric tracing, (B) cephalometric landmarks and the lines connecting them that are referred to as cephalometric reference planes. The most utilized cephalometric landmarks and planes are depicted. PO: porion; S: sella; N: nasion; OR: orbitale; PNS: posterior nasal spine; ANS: anterior nasal spine; A: A-point, B: B-point, Go: gonion, Pg: pogonion, Gn: gnathion, Me: menton; SN: Anterior cranial base plane; sBa: Posterior cranial base plane; PoOr: Frankfurt horizontal plane; PNS-ANS: Palatal plane; GoMe: Mandibular plane; Y-axis SPg or SGn; NA plane; NB plane; NPg: Facial plane.