Abnormal Dental Phenotypes in GAPO Syndrome: A Descriptive Study with a New Variant & Insights on Teeth Eruption

Overview

Journal Saudi Dent J

Specialty Dentistry

Date 2024 Sep 17

PMID 39286584

Authors

Nermeen El-Moataz Bellah Ahmed

Mostafa I Mostafa

Mohamed S Abdel-Hamid

Mennat Mehrez

Affiliations

Soon will be listed here.

Abstract

Objective: GAPO syndrome is usually diagnosed clinically owing to its characteristic features of growth retardation, alopecia, pseudoanodontia, and ophthalmic anomalies. Pseudoanodontia describes the failure of eruption of the two sets of teeth in these patients. Thus, the abnormal dental phenotype is the emergence of a set or part of a set of dentitions.

Purpose: This study reports the physical, oro-dental, and molecular findings of two new sibs with GAPO syndrome and provides a description of the dental phenotype of one of the patients reported before.

Materials & Methods: The patients were subjected to full medical history taking and three generations-pedigree construction. They were phenotyped according to the elements of morphology: Standard terminology series. After parental consents were acquired, molecular analysis was carried out for the two sibs (Patient 1 & 2).

Results: These included a new gene variant associated with erupted teeth in GAPO syndrome and new clinical features. A new classification for the terminologies of eruption disturbances was suggested.

Conclusion: The study asserts the importance of oro-dental examination and follow-ups as dental updates may occur in these cases.

Citing Articles

Syndromic and Non-Syndromic Primary Failure of Tooth Eruption: A Genetic Overview.

Modafferi C, Tabolacci E, Grippaudo C, Chiurazzi P Genes (Basel). 2025; 16(2).

PMID: 40004475 PMC: 11855040. DOI: 10.3390/genes16020147.

References

Janssen K, Raghoebar G, Visser A, Vissink A . [Terminology and manifestations of eruption disturbances]. Ned Tijdschr Tandheelkd. 2014; 121(4):218-26. View

Biesecker L, Adam M, Chung B, Kosaki K, Menke L, White S . Elements of morphology: Standard terminology for the trunk and limbs. Am J Med Genet A. 2022; 188(11):3191-3228. PMC: 9582996. DOI: 10.1002/ajmg.a.62965. View

Frazier-Bowers S, Puranik C, Mahaney M . The etiology of eruption disorders - further evidence of a 'genetic paradigm'. Semin Orthod. 2010; 16(3):180-185. PMC: 2933797. DOI: 10.1053/j.sodo.2010.05.003. View

Awad M, Dalbah L, Srirengalakshmi M, Venugopal A, Vaid N . Review and case report of the treatment in a young girl with primary failure of eruption. Clin Case Rep. 2022; 10(3):e05632. PMC: 8931470. DOI: 10.1002/ccr3.5632. View

Demirgunes E, Ersoy-Evans S, Karaduman A . GAPO syndrome with the novel features of pulmonary hypertension, ankyloglossia, and prognathism. Am J Med Genet A. 2009; 149A(4):802-5. DOI: 10.1002/ajmg.a.32686. View

Falcone M, Chang Y, Lidov H, Stagner A, Dagi L . Two siblings with GAPO syndrome: Ophthalmic presentation and histopathologic findings. Ophthalmic Genet. 2023; 44(6):598-601. DOI: 10.1080/13816810.2023.2175225. View

Salas-Alanis J, Scott C, Fajardo-Ramirez O, Duran C, Moreno-Trevino M, Kelsell D . New ANTXR1 Gene Mutation for GAPO Syndrome: A Case Report. Mol Syndromol. 2016; 7(3):160-3. PMC: 4988245. DOI: 10.1159/000446619. View

Proffit W, Frazier-Bowers S . Mechanism and control of tooth eruption: overview and clinical implications. Orthod Craniofac Res. 2009; 12(2):59-66. DOI: 10.1111/j.1601-6343.2009.01438.x. View

Troxell T, Piccinin M, Smith C, Parsons M, Drew G . GAPO syndrome: a rare genodermatosis presenting with unique features. Int J Dermatol. 2018; 57(6):727-728. DOI: 10.1111/ijd.13928. View

10.

Stranecky V, Hoischen A, Hartmannova H, Zaki M, Chaudhary A, Zudaire E . Mutations in ANTXR1 cause GAPO syndrome. Am J Hum Genet. 2013; 92(5):792-9. PMC: 3644626. DOI: 10.1016/j.ajhg.2013.03.023. View

11.

Puranik R, Puranik S, Hallur N, Venkatesh D . GAPO Syndrome-A Rare Cause of Osteomyelitis of Jaws; Report of 4 Cases With a Brief Review of the Literature. J Oral Maxillofac Surg. 2018; 76(6):1216-1225. DOI: 10.1016/j.joms.2017.12.002. View

12.

Raghoebar G, BOERING G, Vissink A, Stegenga B . Eruption disturbances of permanent molars: a review. J Oral Pathol Med. 1991; 20(4):159-66. DOI: 10.1111/j.1600-0714.1991.tb00913.x. View

13.

Bayram Y, Pehlivan D, Karaca E, Gambin T, Jhangiani S, Erdin S . Whole exome sequencing identifies three novel mutations in ANTXR1 in families with GAPO syndrome. Am J Med Genet A. 2014; 164A(9):2328-34. PMC: 4332576. DOI: 10.1002/ajmg.a.36678. View

14.

Tipton R, GORLIN R . Growth retardation, alopecia, pseudo-anodontia, and optic atrophy--the GAPO syndrome: report of a patient and review of the literature. Am J Med Genet. 1984; 19(2):209-16. DOI: 10.1002/ajmg.1320190202. View

15.

Sobacchi C, Schulz A, Coxon F, Villa A, Helfrich M . Osteopetrosis: genetics, treatment and new insights into osteoclast function. Nat Rev Endocrinol. 2013; 9(9):522-36. DOI: 10.1038/nrendo.2013.137. View

16.

de La Dure-Molla M, Fournier B, Manzanares M, Acevedo A, Hennekam R, Friedlander L . Elements of morphology: Standard terminology for the teeth and classifying genetic dental disorders. Am J Med Genet A. 2019; 179(10):1913-1981. DOI: 10.1002/ajmg.a.61316. View

17.

Bacon W, Hall R, Roset J, Boukari A, Tenenbaum H, Walter B . GAPO syndrome: a new case of this rare syndrome and a review of the relative importance of different phenotypic features in diagnosis. J Craniofac Genet Dev Biol. 2000; 19(4):189-200. View

18.

Ahmed B, Gritli S . Telogen hair loss and androgenetic-like alopecia in GAPO syndrome. Australas J Dermatol. 2018; 60(2):e142-e144. DOI: 10.1111/ajd.12937. View

19.

Abdel-Hamid M, Ismail S, Zaki M, Abdel-Salam G, Otaify G, Issa M . GAPO syndrome in seven new patients: Identification of five novel ANTXR1 mutations including the first large intragenic deletion. Am J Med Genet A. 2018; 179(2):237-242. DOI: 10.1002/ajmg.a.61021. View

20.

Dinckan N, Du R, Akdemir Z, Bayram Y, Jhangiani S, Doddapaneni H . A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis. Am J Med Genet A. 2018; 176(4):1015-1022. PMC: 5933053. DOI: 10.1002/ajmg.a.38625. View