Fahr's Syndrome with Pseudohypoparathyroidism: Oral Features and Genetic Insights

Abstract

Fahr's syndrome is a rare neurodegenerative disorder with limited research on its oral manifestations. This study investigates the dental features and genetic background of Fahr's syndrome through a pedigree analysis and a retrospective literature study. A clinical examination and whole-exome sequencing (WES) were conducted on a female patient with Fahr's syndrome and pseudohypoparathyroidism, along with her family members. The patient presented with super-numerary teeth, tooth agenesis, enamel hypoplasia, and abnormal tooth eruption. The WES did not reveal any known pathogenic mutations related to pseudohypoparathyroidism or Fahr's disease. However, genetic variations in KIF1A, FZD8, and PDGFA may underlie these dental abnormalities. Additionally, a retrospective analysis of 22 reported cases from PubMed and the Human Gene Mutation Database (1 January 1965-30 June 2024) was conducted with keywords such as "Fahr's disease", "Fahr's syndrome", "dental", and "hypoparathyroidism". The analysis showed that patients with Fahr's syndrome, pseudohypoparathyroidism, and idiopathic hypoparathyroidism exhibited similar oral abnormalities, including tooth agenesis, root dysplasia, dental malformations, and abnormal tooth eruption. Variations in the incidence of tooth agenesis and dental malformation among these groups may be linked to differences in parathyroid hormone metabolism. These findings suggest oral abnormalities are the key local features of Fahr's syndrome and related parathyroid disorders.

Keywords: Fahr’s syndrome; oral clinical features; pseudohypoparathyroidism.

Figure 1

Oral examination of the proband revealed multiple unerupted teeth. The left upper deciduous canine and the right lower deciduous canine (root remnant) were retained. Additionally, enamel hypoplasia was observed in the right upper second premolar, right lower first premolar, and left lower first premolar.

Figure 2

Noncontrast computed tomography images of the head revealed calcifications in the bilateral basal ganglia, encompassing the caudate nucleus, putamen, globus pallidus, thalamus, and dentate nuclei. The black dashed arrows in the figure indicate areas of calcification.

Figure 3

(A) CBCT imaging of the proband revealed multiple impacted teeth, with the absence of the lower right second molar (marked with “×” in the figure). Additionally, a supernumerary tooth was identified on the palatal side between the upper right canine and the first premolar (denoted by “△”). (B) Developmental anomalies were observed in the roots of the lower left canine, first and second premolars, and in the lower right canine, first premolar, and second molar (indicated by “*”). Retained deciduous teeth are marked in blue, corresponding to the upper left deciduous canine and the residual root of the lower right deciduous canine.

Figure 4

The family genealogy diagram of this study includes the proband’s father (I1), mother (I2), two older brothers (II1, II2), and the proband (II3).