Phenotypic and Molecular Heterogeneity in Mandibulofacial Dysostoses: A Case Series From India

Abstract

Objective

Facial dysostosis is a group of rare craniofacial congenital disabilities requiring multidisciplinary long-term care. This report presents the phenotypic and genotypic information from South India.

Design

The study is a case series.

Setting

This was an international collaborative study involving a tertiary craniofacial clinic and medical genetics unit.

Patients, Participants

The participants were 9 families with 17 affected individuals of facial dysostosis.

Intervention

Exome analysis focused on known genes associated with acrofacial and mandibulofacial syndromes.

Main Outcome Measure

The outcome measure was to report phenotyptic and genetic heterogeneity in affected individuals.

Results

A Tessier cleft was seen in 7 (41%), lower eyelid coloboma in 12 (65%), ear anomalies in 10 (59%), uniolateral or bilateral aural atresia in 4 (24%), and deafness in 6 (35%). The facial gestalt of Treacher Collins syndrome (TCS) showed extensive phenotypic variations. Pathogenic variants in TCOF1 (Treacher Collins syndrome) were seen in six families, POLR1A (acrofacial dysostosis, Cincinnati type) and EFTUD2 (mandibulofacial dysostosis with microcephaly) in one each. One family (11.1%) had no detectable variation. Five out of six probands with Treacher Collins syndrome had other affected family members (83.3%), including a non-penetrant mother, identified after sequencing.

Conclusion

Our report illustrates the molecular heterogeneity of mandibulofacial dysostosis in India.

Keywords

acrofacial dysostosis familial mandibulofacial dysostosis with microcephaly maxillary hypoplasia Treacher Collins syndrome

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References

Abell

Hopkin

Bender

, Jackson F, Smallwood K, Sullivan B, Stottman RW, Saal HM, Weaver KN. Mandibulofacial dysostosis with microcephaly: an expansion of the phenotype via parental survey. Am J Med Genet Part A. 2021;185(2):413-423.

Chen

Guo

, Shan J, Xu HS, Li JY, Sun S, Hao SJ, Jin L, Chai G, et al. Mutation screening of Chinese Treacher Collins syndrome patients identified novel TCOF1 mutations. Mol Genet Genomics. 2018;293(2):569-577.

Ellis

Dawson

Dixon

. Mutation testing in Treacher Collins syndrome. J Orthod. 2002;29(4):293-297.

Hennekam

RCM

Krantz

Allanson

. Gorlin’s syndromes of the head and neck. 5th ed. Oxford, UK: Oxford University Press; 2010: 889-893.

Horiuchi

Ariga

Fujioka

, Kawashima K, Yamamoto Y, Igawa H, Sugihara T, Sakiyama Y. Mutational analysis of the TCOF1 gene in 11 Japanese patients with Treacher Collins syndrome and mechanism of mutagenesis. Am J Med Genet A. 2005;134(4):363-367.

Kantaputra

Tripuwabhrut

Intachai

, Carlson BM, Quarto N, Ngamphiw C, Tongsima S, Sonsuwan N. Treacher Collins syndrome: a novel TCOF1 mutation and monopodial stapes. Clin Otolaryngol. 2020;45(5):695-702.

Lehalle

Wieczorek

Zechi-Ceide

, Passos-Bueno MR, Lyonnet S, Amiel J, Gordon CT. A review of craniofacial disorders caused by spliceosomal defects. Clin Genet. 2015;88(5):405-415.

Smith

Fowler

Ellis

. Long-term treatment outcomes from a patient’s perspective with Treacher Collins syndrome. BMJ Case Rep. 2021;14:e241351. doi:10.1136/bcr-2020-241351.

Splendore

Silva

Alonso

, Richieri-Costa A, Alonso N, Rosa A, Carakushanky G, Cavalcanti DP, Brunoni D, Passos-Bueno MR. High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes. Hum Mutat. 2000;16(4):315-322.

10.

Teber

Gillessen-Kaesbach

Fischer

, Böhringer S, Albrecht B, Albert A, Arslan-Kirchner M, Haan E, Hagedorn-Greiwe M, Hammans C, et al. Genotyping in 46 patients with tentative diagnosis of Treacher Collins syndrome revealed unexpected phenotypic variation. Eur J Hum Genet. 2004;12(11):879-890.

11.

Terrazas

Dixon

Trainor

Dixon

. Rare syndromes of the head and face: mandibulofacial and acrofacial dysostoses. WIREs Dev Biol. 2017;6:e263. doi:10.1002/wdev.263.

12.

Trainor

. Craniofacial birth defects: the role of neural crest cells in the etiology and pathogenesis of Treacher Collins syndrome and the potential for prevention. Am J Med Genet A. 2010;152A(12):2984-2994.

13.

Vincent

Geneviève

Ostertag

, Marlin S, Lacombe D, Martin-Coignard D, Coubes C, David A, Lyonnet S, Vilain C, et al. Treacher Collins syndrome: a clinical and molecular study based on a large series of patients. Genet Med. 2016;18(1):49-56.

14.

Weaver

Watt

Hufnagel

, Acedo JN, Linscott LL, Sund KL, Bender PL, König R, Lourenco CM, Hehr U, et al. Acrofacial dysostosis, Cincinnati type, a mandibulofacial dysostosis syndrome with limb anomalies, Is caused by POLR1A dysfunction. Am J Hum Genet. 2015;96(5):765-774.

15.

KPT

Luk

Gordon

, Fung G, Oufadem M, Garcia-Barcelo MM, Amiel J, Chung BHY, Lo FMI, Toing YT. Mandibulofacial dysostosis Guion-Almeida type caused by novel EFTUD2 splice site variants in two Asian children. Clin Dysmorphol. 2018;27(2):31-35.

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