Role of primary cilia and Hedgehog signaling in craniofacial features of Ellis-van Creveld syndrome.

Ellis-van Creveld syndrome (EvC) is an autosomal recessive genetic disorder involving pathogenic variants of EVC and EVC2 genes and classified as a ciliopathy. The syndrome is caused by mutations in the EVC gene on chromosome 4p16, and EVC2 gene, located close to the EVC gene, in a head-to-head configuration. Regardless of the affliction of EVC or EVC2, the clinical features of Ellis-van Creveld syndrome are similar. Both these genes are expressed in tissues such as, but not limited to, the heart, liver, skeletal muscle, and placenta, while the predominant expression in the craniofacial tissues is that of EVC2. Biallelic mutations of EVC and EVC2 affect Hedgehog signaling and thereby ciliary function, crucial factors in vertebrate development, culminating in the phenotypical features characteristic of EvC. The clinical features of Ellis-van Creveld syndrome are consistent with significant abnormalities in morphogenesis and differentiation of the affected tissues. The robust role of primary cilia in histodifferentiation and morphodifferentiation of oral, perioral, and craniofacial tissues is becoming more evident in the most recent literature. In this review, we give a summary of the mechanistic role of primary cilia in craniofacial development, taking Ellis-van Creveld syndrome as a representative example.

Monckeberg's Medial Sclerosis as a Cause for Headache and Facial Pain.

PURPOSE OF REVIEW: Mönckeberg's medial sclerosis (MMS) is a chronic, non-inflammatory degenerative condition affecting primarily the tunica media of muscular arteries resulting in their calcification. The purpose of this comprehensive review is to describe MMS as it appears in the literature, in the context of headache and facial pain. Understanding the etiopathology, the associated conditions, and the differential diagnoses is important in managing MMS. RECENT FINDINGS: Management of MMS primarily depends upon identification of its associated conditions and their treatment. Due to the rare incidence and inadequate literature on MMS presenting with headaches, the diagnosis of the pain and the entity itself is challenging. MMS is characterized by associated systemic conditions and absence of inflammatory markers. It can mimic giant cell arteritis (GCA) and other pain entities. An interdisciplinary approach involving appropriate specialties is recommended.