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. 2022 Jun 9:13:875490.
doi: 10.3389/fgene.2022.875490. eCollection 2022.

Oral Phenotype of Singleton-Merten Syndrome: A Systematic Review Illustrated With a Case Report

Margot Charlotte Riou  1   2   3 , Muriel de La Dure-Molla  2   3   4 , Stéphane Kerner  2   3 , Sophie Rondeau  5 , Adrien Legendre  6 , Valerie Cormier-Daire  4 , Benjamin P J Fournier  1   2   3
Affiliations

Oral Phenotype of Singleton-Merten Syndrome: A Systematic Review Illustrated With a Case Report

Margot Charlotte Riou et al. Front Genet. .

Abstract

Background: Singleton-Merten syndrome type 1 (SGMRT1) is a rare autosomal dominant disorder caused by IFIH1 variations with blood vessel calcifications, teeth anomalies, and bone defects. Aim: We aimed to summarize the oral findings in SGMRT1 through a systematic review of the literature and to describe the phenotype of a 10-year-old patient with SGMRT1 diagnosis. Results: A total of 20 patients were described in the literature, in nine articles. Eight IFIH1 mutations were described in 11 families. Delayed eruption, short roots, and premature loss of permanent teeth were the most described features (100%). Impacted teeth (89%) and carious lesions (67%) were also described. Our patient, a 10-year-old male with Singleton-Merten syndrome, presented numerous carious lesions, severe teeth malposition, especially in the anterior arch, and an oral hygiene deficiency with a 100% plaque index. The panoramic X-ray did not show any dental agenesis but revealed very short roots and a decrease in the jaw alveolar bone height. The whole-genome sequencing analysis revealed a heterozygous de novo variant in IFIH1 (NM_022168.4) c.2465G > A (p.Arg822Gln). Conclusion: Confused descriptions of oral features occurred in the literature between congenital findings and "acquired" pathology, especially carious lesions. The dental phenotype of these patients encompasses eruption anomalies (delayed eruption and impacted teeth) and lack of root edification, leading to premature loss of permanent teeth, and it may contribute to the diagnosis. An early diagnosis is essential to prevent teeth loss and to improve the quality of life of these patients. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022300025].

Keywords: Singleton–Merten syndrome; genetics; oral physiopathology; rare diseases; type 1 interferonopathy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of PRISMA.
FIGURE 2
FIGURE 2
Visualization of the SMGRT1 mutations in MDA5. Plots of all disease-causing mutations in MDA5 associated to SGMRT1. The conservation score is between 0 and 1, with 0 indicating no other sequences matching the reference (Homo sapiens NP_071451.2) at the position, and 1 indicating all sequences matching the reference at that position. CARD1: caspase activation and recruitment domain found in MDA5, first repeat; CARD2: caspase activation and recruitment domain found in MDA5, second repeat; DEXHC: DEXH-box helicase domain of RLR-2; MDA5_ID: insert domain of MDA5; SF2: C-terminal helicase domain of the endoribonuclease dicer; MDA_C: C-terminal domain of melanoma differentiation-associated protein 5. The hotspot is represented in orange.
FIGURE 3
FIGURE 3
Case report. (A) Orthopantomogram X-ray of our 10-year-old Singleton-Merten patient. In orange, a first permanent molar (tooth n°46) and central permanent mandibular incisors (teeth n° 31–41) with short roots were highlighted. To compare, a healthy patient’s teeth are shown in a green insert. (B) Photography of the patient. (C,D) Intra-oral photographies of the maxillary and the mandibular arch. (E) First molar enamel. (F) Second temporary molar dentin. (G) First molar cement.
See this image and copyright information in PMC

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