{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:31:55Z","timestamp":1790271115333,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,3,23]],"date-time":"2016-03-23T00:00:00Z","timestamp":1458691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Auriculo\u2010Condylar Syndrome (ACS) is a craniofacial malformation syndrome characterized by external ear anomalies, hypoplasia of the mandibular condyle, temporomandibular joint abnormalities, micrognathia, and microstomia. Glossoptosis, masticatory abnormalities, orthodontic problems, and malocclusion occur in a majority of affected subjects. The clinical diagnosis is usually suggested by the pathognomonic ear appearance (\u201cquestion mark ear\u201d), consisting of a variable degree of clefting between the helix and earlobe. The genetic mechanisms underlying ACS have recently been identified. Both autosomal dominant and recessive inheritance of mutations in phospholipase C, beta 4 (<jats:italic>PLCB4<\/jats:italic>) and endothelin 1 (<jats:italic>EDN1<\/jats:italic>) have been reported along with autosomal dominant mutations in guanine nucleotide\u2010binding protein (G protein) \u03b1 inhibiting activity polypeptide 3 (<jats:italic>GNAI3<\/jats:italic>). We report 6 years of follow\u2010up of a child with a clinical phenotype consistent with ACS due to a homozygous frameshift mutation in <jats:italic>PLCB4<\/jats:italic>. The baby presented feeding difficulties associated with failure to thrive and a complex sleep\u2010related respiratory disorder, characterized by central and obstructive apnoeas. Our observations of this case further delineate the phenotype of ACS associated with autosomal recessive <jats:italic>PLCB4<\/jats:italic> loss\u2010of\u2010function mutations, underscoring gastrointestinal dysfunction and severe sleep\u2010related breathing abnormalities as additional features when compared to patients with heterozygous mutations with a presumed dominant negative effect. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37625","type":"journal-article","created":{"date-parts":[[2016,3,23]],"date-time":"2016-03-23T13:38:41Z","timestamp":1458740321000},"page":"1471-1478","source":"Crossref","is-referenced-by-count":18,"title":["Respiratory and gastrointestinal dysfunctions associated with auriculo\u2010condylar syndrome and a homozygous PLCB4 loss\u2010of\u2010function mutation"],"prefix":"10.1002","volume":"170","author":[{"given":"Chiara","family":"Leoni","sequence":"first","affiliation":[{"name":"Department of Pediatrics Center for Rare 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