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. 2024 Apr 9;19(1):152.
doi: 10.1186/s13023-024-03142-9.

Genotype-phenotype associations in microtia: a systematic review

Siti Isya Wahdini  1 , Fina Idamatussilmi  1 , Rachmaniar Pramanasari  2 , Almas Nur Prawoto  2 , Citrawati Dyah Kencono Wungu  3 , Indri Lakhsmi Putri  2 , Gunadi  4
Affiliations

Genotype-phenotype associations in microtia: a systematic review

Siti Isya Wahdini et al. Orphanet J Rare Dis. .

Abstract

Background: Microtia is a congenital ear malformation that can occur as isolated microtia or as part of a syndrome. The etiology is currently poorly understood, although there is strong evidence that genetics has a role in the occurrence of microtia. This systematic review aimed to determine the genes involved and the abnormalities in microtia patients' head and neck regions.

Methods: We used seven search engines to search all known literature on the genetic and phenotypic variables associated with the development or outcome of microtia. The identified publications were screened and selected based on inclusion and exclusion criteria and assessed for methodological quality using the Joanna Briggs Institute (JBI) critical appraisal tools. We found 40 papers in this systematic review with phenotypic data in microtia involving 1459 patients and 30 articles containing genetic data involved in microtia.

Result: The most common accompanying phenotype of all microtia patients was external ear canal atresia, while the most common head and neck abnormalities were the auricular, mental, and oral regions. The most common syndrome found was craniofacial microsomia syndrome. In the syndromic microtia group, the most common genes were TCOF1 (43.75%), SIX2 (4.69%), and HSPA9 (4.69%), while in the non-syndromic microtia group, the most frequently found gene was GSC exon 2 (25%), FANCB (16.67%), HOXA2 (8.33%), GSC exon 3 (8.33%), MARS1 (8.33%), and CDT1 (8.33%).

Conclusions: Our systematic review shows some genes involved in the microtia development, including TCOF1, SIX2, HSPA9, GSC exon 2, FANCB, HOXA2, GSC exon 3, MARS1, and CDT1 genes. We also reveal a genotype-phenotype association in microtia. In addition, further studies with more complete and comprehensive data are needed, including patients with complete data on syndromes, phenotypes, and genotypes.

Keywords: CDT1; FANCB; GSC exon 2; GSC exon 3; HOXA2; HSPA9; MARS; SIX2; TCOF1; Genotype- phenotype association; Microtia; Non-syndromic; Syndromic.

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Conflict of interest statement

The authors declared no potential conflicts of interest concerning this article's research, authorship, and publication.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram of the study inclusion process
Fig. 2
Fig. 2
Patient age characteristics (n= 39)
Fig. 3
Fig. 3
Demographics of origin of patients stratified by continent (n= 1459) (basic continent classifications refer to the UNSD Methodology) [72]
Fig. 4
Fig. 4
Other phenotypes accompany microtia in the head and neck region
Fig. 5
Fig. 5
All genes involved in the occurrence of microtia
See this image and copyright information in PMC

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