Severe Unilateral Microtia with Aural Atresia, Hair White Patch, Stereotypes in a Young Boy with De novo 16p13.11 Deletion: Reasons for a New Genotype–Phenotype Correlation

Piero Pavone; Xena Giada Pappalardo; Claudia Parano; Enrico Parano; Antonio Corsello; Martino Ruggieri; Giovanni Cacciaguerra; Raffaele Falsaperla

doi:10.1055/s-0043-1777362

Global Medical Genetics, Inhaltsverzeichnis

CC BY 4.0 · Glob Med Genet 2023; 10(04): 370-375
DOI: 10.1055/s-0043-1777362

Case Report

Severe Unilateral Microtia with Aural Atresia, Hair White Patch, Stereotypes in a Young Boy with De novo 16p13.11 Deletion: Reasons for a New Genotype–Phenotype Correlation

Authors

Piero Pavone^*

¹Section of Paediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
Xena Giada Pappalardo^*

²Unit of Catania, Institute for Biomedical Research and Innovation, National Council of Research, Catania, Italy
Claudia Parano

³Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy
Enrico Parano

²Unit of Catania, Institute for Biomedical Research and Innovation, National Council of Research, Catania, Italy
Antonio Corsello

⁴Neonatal Intensive Care Unit, Department of Sciences for Health Promotion, Maternal Infant Care, Internal Medicine and Medical Specialties “G. D'Alessandro,” University Hospital “P. Giaccone,” Palermo, Italy
Martino Ruggieri

⁵Section of Paediatrics and Child Neuropsychiatry, Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
Giovanni Cacciaguerra

⁵Section of Paediatrics and Child Neuropsychiatry, Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
Raffaele Falsaperla

⁶Neonatal Intensive Care Unit, AUO Policlinico “Rodolico-San Marco,” University of Catania, Catania, Italy

⁷Acute End Emergency Pediatric Unit, Department of General Pediatrics, AUO Policlinico “Rodolico-San Marco,” University of Catania, Catania, Italy

Abstract

Background Microtia is an uncommon congenital malformation ranging from mild anatomic structural abnormalities to partial or complete absence of the ear leading to hearing impairment. Congenital microtia may present as a single malformation (isolated microtia) or sometimes associated with other congenital anomalies involving various organs. Microtia has been classified in three degrees according to the complexity of the auricular malformation and to anotia referred to the total absence of the ear. Genetic role in causing auricular malformation has been widely demonstrated, and genotype–phenotype correlation has been reported in cases of syndromic microtia.

Case Presentation We report here a young patient with a third degree of scale classification and aural atresia. The patient showed unspecific facial dysmorphism, speech delay, precocious teething, hair white patch, and stereotypic anomalous movements. Genetic analysis displayed a de novo 16p13.11 deletion.

Conclusion Microtia with aural atresia is an uncommon and severe birth defect, which affects functional and esthetic aspects, often associated with other malformations. As traumatic this disorder may be for the parents, the microtia and aural atresia are treatable, thanks to the improving and evolving surgical techniques. Based on the genetic analysis and the clinical features observed in the present case, a genotype–phenotype correlation has been proposed.

Keywords

case report - microtia - 16p13.11 deletion - genotype–phenotype correlation

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Referenzen

References
1 Eavey RD. Ear malformations. What a pediatrician can do to assist with auricular reconstruction. Pediatr Clin North Am 1996; 43 (06) 1233-1244
2 Andrews J, Kopacz AA, Hohman MH. Ear microtia. [Updated 2023 Mar 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Jan-. Available at: https://www.ncbi.nlm.nih.gov/books/NBK563243/
3 Luquetti DV, Leoncini E, Mastroiacovo P. Microtia-anotia: a global review of prevalence rates. Birth Defects Res A Clin Mol Teratol 2011; 91 (09) 813-822
4 Canfield MA, Langlois PH, Nguyen LM, Scheuerle AE. Epidemiologic features and clinical subgroups of anotia/microtia in Texas. Birth Defects Res A Clin Mol Teratol 2009; 85 (11) 905-913
5 Cox TC, Camci ED, Vora S, Luquetti DV, Turner EE. The genetics of auricular development and malformation: new findings in model systems driving future directions for microtia research. Eur J Med Genet 2014; 57 (08) 394-401
6 Harris J, Källén B, Robert E. The epidemiology of anotia and microtia. J Med Genet 1996; 33 (10) 809-813
7 Al-Sulaimani AK, Al-Khabori MS, Haridi KM, Al-Busaidi SS. Prevalence and characteristics of microtia in Oman: 37 Years analysis. J Plast Reconstr Aesthet Surg 2023; 76: 292-294
8 Ma J, Zhou W-H. [Genetic characteristics of microtia-associated syndromes in neonates]. Zhongguo Dang Dai Er Ke Za Zhi 2022; 24 (06) 614-619
9 Estandia-Ortega B, Reyna-Fabián ME, Velázquez-Aragón JA, González-Del Angel A, Fernández-Hernández L, Alcántara-Ortigoza MA. The enigmatic etiology of oculo-auriculo-vertebral spectrum (OAVS): an exploratory gene variant interaction approach in candidate genes. Life (Basel) 2022; 12 (11) 1723
10 Quinn S, Kavanagh K, McArdle L, Betts D, Lynch S-A. Unilateral microtia found in association with a de-novo 20q13.33 deletion, is there a causal link?. Clin Dysmorphol 2023; 32 (01) 39-42
11 Gendron C, Schwentker A, van Aalst JA. Genetic advances in the understanding of microtia. J Pediatr Genet 2016; 5 (04) 189-197
12 Lu M, Lu X, Jiang H, Pan B. Review of preferential suspicious genes in microtia patients through various approaches. J Craniofac Surg 2020; 31 (02) 538-541
13 Luquetti DV, Heike CL, Hing AV, Cunningham ML, Cox TC. Microtia: epidemiology and genetics. Am J Med Genet A 2012; 158A (01) 124-139
14 Kohlhase J. SALL1 mutations in Townes-Brocks syndrome and related disorders. Hum Mutat 2000; 16 (06) 460-466
15 Celse T, Tingaud-Sequeira A, Dieterich K. et al. OTX2 duplications: a recurrent cause of oculo-auriculo-vertebral spectrum. J Med Genet 2023; 60 (06) 620-626
16 Hao S, Jin L, Li C. et al. Mutational analysis of GSC, HOXA2 and PRKRA in 106 Chinese patients with microtia. Int J Pediatr Otorhinolaryngol 2017; 93: 78-82
17 Quiat D, Timberlake AT, Curran JJ. et al. Damaging variants in FOXI3 cause microtia and craniofacial microsomia. Genet Med 2023; 25 (01) 143-150
18 Aguinaga-Ríos M, Frías S, Arenas-Aranda DJ, Morán-Barroso VF. [Microtia-atresia: clinical, genetic and genomic aspects]. Bol Méd Hosp Infant México 2014; 71 (06) 387-395
19 Bartel-Friedrich S. Congenital auricular malformations: description of anomalies and syndromes. Facial Plast Surg 2015; 31 (06) 567-580
20 Veltman JA, Jonkers Y, Nuijten I. et al. Definition of a critical region on chromosome 18 for congenital aural atresia by arrayCGH. Am J Hum Genet 2003; 72 (06) 1578-1584
21 Tropeano M, Andrieux J, Collier DA. Clinical utility gene card for: 16p13.11 microdeletion syndrome. Eur J Hum Genet 2014; 22 (05)
22 Tan L, Bi B, Zhao P. et al. Severe congenital microcephaly with 16p13.11 microdeletion combined with NDE1 mutation, a case report and literature review. BMC Med Genet 2017; 18 (01) 141
23 Smith AE, Jnah A, Newberry D. Chromosome 16p13.11 microdeletion syndrome in a newborn: a case study. Neonatal Netw 2018; 37 (05) 303-309
24 Hunter M, Spiller KJ, Dominique MA. et al. Microglial transcriptome analysis in the rNLS8 mouse model of TDP-43 proteinopathy reveals discrete expression profiles associated with neurodegenerative progression and recovery. Acta Neuropathol Commun 2021; 9 (01) 140
25 Veugen CCAFM, Dikkers FG, de Bakker BS. The developmental origin of the auricula revisited. Laryngoscope 2020; 130 (10) 2467-2474
26 Chen X, Xu Y, Li C. et al. Key genes identified in nonsyndromic microtia by the analysis of transcriptomics and proteomics. ACS Omega 2022; 7 (20) 16917-16927
27 Granata P, Cocciadiferro D, Zito A. et al. Whole exome sequencing in 16p13.11 microdeletion patients reveals new variants through deductive and systems medicine approaches. Front Genet 2022; 13: 798607
28 Arslan AB, Zamani AG, Yıldırım MS. Novel findings, mini-review and dysmorphological characterization of 16p13.11 microduplication syndrome. Int J Dev Neurosci 2022; 82 (04) 289-294
29 Truong MT, Liu Y-CC, Kohn J. et al. Integrated microtia and aural atresia management. Front Surg 2022; 9: 944223
30 Patel KR, Benchetrit L, Ronner EA. et al. Development of an interdisciplinary microtia-atresia care model: a single-center 20-year experience. Laryngoscope Investig Otolaryngol 2022; 7 (06) 2103-2111
31 Ullmann R, Turner G, Kirchhoff M. et al. Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation. Hum Mutat 2007; 28 (07) 674-682
32 Hannes FD, Sharp AJ, Mefford HC. et al. Recurrent reciprocal deletions and duplications of 16p13.11: the deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant. J Med Genet 2009; 46 (04) 223-232
33 Heinzen EL, Arzimanoglou A, Brashear A. et al; ATP1A3 Working Group. Distinct neurological disorders with ATP1A3 mutations. Lancet Neurol 2014; 13 (05) 503-514