Auriculocondylar syndrome: Pathogenesis, clinical manifestations and surgical therapies

Li, Qingqing; Jiang, Zhiyuan; Zhang, Liyuan; Cai, Zhen

doi:10.1016/j.jfma.2023.04.024

Cited by 7 publications

(4 citation statements)

References 77 publications

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“…Dominant mutations, including rs397514481, cause the disease through dominant-negative effects on the endothelin receptor type A-Gq/11 pathway important for forming lower jaw and middle ear structures during embryonic development (Kanai et al 2022 ). Auriculocondylar syndrome 2 is characterized by craniofacial anomalies and other less frequent features, including speech delay (Li et al 2023 ). Variable expressivity and incomplete penetrance have also been observed in auriculocondylar syndrome 2 (Vegas et al 2022 ).…”

Section: Resultsmentioning

confidence: 99%

Whole exome sequencing and polygenic assessment of a Swedish cohort with severe developmental language disorder

Yahia,

Li,

Lejerkrans

et al. 2024

Hum. Genet.

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Developmental language disorder (DLD) overlaps clinically, genetically, and pathologically with other neurodevelopmental disorders (NDD), corroborating the concept of the NDD continuum. There is a lack of studies to understand the whole genetic spectrum in individuals with DLD. Previously, we recruited 61 probands with severe DLD from 59 families and examined 59 of them and their families using microarray genotyping with a 6.8% diagnostic yield. Herein, we investigated 53 of those probands using whole exome sequencing (WES). Additionally, we used polygenic risk scores (PRS) to understand the within family enrichment of neurodevelopmental difficulties and examine the associations between the results of language-related tests in the probands and language-related PRS. We identified clinically significant variants in four probands, resulting in a 7.5% (4/53) molecular diagnostic yield. Those variants were in PAK2, MED13, PLCB4, and TNRC6B. We also prioritized additional variants for future studies for their role in DLD, including high-impact variants in PARD3 and DIP2C. PRS did not explain the aggregation of neurodevelopmental difficulties in these families. We did not detect significant associations between the language-related tests and language-related PRS. Our results support using WES as the first-tier genetic test for DLD as it can identify monogenic DLD forms. Large-scale sequencing studies for DLD are needed to identify new genes and investigate the polygenic contribution to the condition.

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Section: Resultsmentioning

confidence: 99%

Whole exome sequencing and polygenic assessment of a Swedish cohort with severe developmental language disorder

Yahia,

Li,

Lejerkrans

et al. 2024

Hum. Genet.

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“…(Gordon, Petit, et al., 2013 ; Kido et al., 2013 ; Leoni et al., 2016 ; Masotti et al., 2007 ; Rieder et al., 2012 ; Romanelli et al., 2015 ). The most commonly mutated gene in individuals with ARCND is PLCB4 gene (Li et al., 2023 ; Vegas et al., 2022 ) which was reported in only about 36 cases worldwide.…”

Section: Introductionmentioning

confidence: 99%

Auriculocondylar syndrome 2 caused by a novel PLCB4 variant in a male Chinese neonate: A case report and review of the literature

Zhang,

Zhao,

Dai

et al. 2024

Molec Gen & Gen Med

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BackgroundAuriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457).MethodsThis study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2.ResultsThe proband, a 5‐day‐old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio‐based whole‐exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved.ConclusionAs with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long‐term follow‐up and assessment are still required.

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“…The typical triad manifestations of ARCND include question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia [ 2 ]. Other facial abnormalities [ 3 ] in the hearing [ 4 ], respiratory [ 5 ], digestive [ 6 ], reproductive [ 7 ], and even developmental [ 5 ] systems have also been reported. However, differences in gene expression have led to a wide range of differences in the clinical phenotypes between individuals and their families [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Novel GNAI3 mutation in a Chinese family with auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report

Shi,

Rong,

Liu

et al. 2024

BMC Oral Health

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Background Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition that typically manifests as question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. Severe dental and maxillofacial malformations present considerable challenges in patients’ lives and clinical treatment. Currently, only a few ARCND cases have been reported worldwide, but most of them are related to genetic mutations, clinical symptoms, and ear correction; there are few reports concerning the treatment of dentofacial deformities. Case presentation Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient’s dentofacial deformity. A good prognosis was achieved at the 5-year follow-up, and the patient returned to normal life. Conclusions ARCND is a monogenic and rare condition that can be diagnosed based on its clinical triad of core features. Molecular diagnosis plays a crucial role in the diagnosis of patients with inconspicuous clinical features. We present a novel insertion variation in GNAI3, which was identified in exon 2 of chromosome 110116384 in a Chinese family. Sequential therapy with preoperative orthodontic treatment combined with distraction osteogenesis and orthognathic surgery guided by 3D digital technology may be a practical and effective method for treating ARCND.

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Auriculocondylar syndrome: Pathogenesis, clinical manifestations and surgical therapies

Cited by 7 publications

References 77 publications

Whole exome sequencing and polygenic assessment of a Swedish cohort with severe developmental language disorder

Whole exome sequencing and polygenic assessment of a Swedish cohort with severe developmental language disorder

Auriculocondylar syndrome 2 caused by a novel PLCB4 variant in a male Chinese neonate: A case report and review of the literature

Novel GNAI3 mutation in a Chinese family with auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report

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