Abnormalities in pharyngeal arch‐derived structures in SATB2‐associated syndrome

• Published in: Clinical genetics 2024-08, Vol.106 (2), p.209-213
• Main Authors: Zarate, Yuri A., Bosanko, Katherine, Derar, Nada, Fish, Jennifer L.
• Format: Article
• Language: English
• Subjects: Animals; Branchial Region - abnormalities; Branchial Region - pathology; Children; Craniofacial Abnormalities - genetics; Craniofacial Abnormalities - pathology; craniofacial anomalies; Craniofacial growth; Developmental stages; Embryogenesis; Female; Ganglia; Hereditary diseases; Humans; Jaw; Male; Mandible; Mandible - abnormalities; Mandible - pathology; Matrix Attachment Region Binding Proteins - genetics; Matrix Attachment Region Binding Proteins - metabolism; Mesenchyme; Mice; Mice, Knockout; Mutants; Neurodevelopmental disorders; pharyngeal arches; Pharynx; Phenotype; Phenotypes; SATB2; SATB2‐associated syndrome; Syndrome; Transcription Factors - genetics; Trigeminal ganglion
• ISSN: 0009-9163; 1399-0004; 1399-0004
• DOI: 10.1111/cge.14540

SATB2‐associated syndrome (SAS, glass syndrome, OMIM#612313) is a neurodevelopmental autosomal dominant disorder with frequent craniofacial abnormalities including palatal and dental anomalies. To assess the role of Satb2 in craniofacial development, we analyzed mutant mice at different stages of development. Here, we show that Satb2 is broadly expressed in early embryonic mouse development including the mesenchyme of the second and third arches. Satb2−/− mutant mice exhibit microglossia, a shortened lower jaw, smaller trigeminal ganglia, and larger thyroids. We correlate these findings with the detailed clinical phenotype of four individuals with SAS and remarkable craniofacial phenotypes with one requiring mandibular distraction in childhood. We conclude that the mouse and patient data presented support less well‐described phenotypic aspects of SAS including mandibular morphology and thyroid anatomical/functional issues. We explore the roles of Satb2 in head development and correlate with the clinical presentation of individuals with SATB2‐associated syndrome with remarkable phenotypes of the craniofacial skeleton. The data presented support less well‐described phenotypic aspects of SAS including mandibular morphology and thyroid anatomical/functional issues.