TWIST1 Gene Variants Cause Craniosynostosis with Limb Abnormalities in Asian Patients

Abstract

The TWIST1 gene codes for a highly conserved transcription factor in a basic helix–loop–helix transcription factors family. The pattern of inheritance is autosomal dominant in Saethre–Chotzen syndrome, Robinow–Sorauf syndrome, and Sweeney–Cox syndrome. Major features of these syndromes include coronal synostosis, vision problems, and deafness, and facial features include hypertelorism, low-set ears, arched eyebrows, beaked nose, maxillary hypoplasia, and other dysmorphisms including broad great toes, clinodactyly, brachydactyly, and cutaneous syndactyly. TWIST1 (bHLH) transcription factor regulates the formation of head and limbs in the embryo. We describe three families affected with craniosynostosis in whom a sporadic TWIST1 variant was identified on whole exome sequencing, chromosomal microarray, and Sanger sequencing.

Keywords

craniosynostosis - craniofacial - SCS - syndactyly - ptosis

Data Availability Statement

The data of the patients can be obtained from the corresponding author and has not been given publicly due to privacy or ethical restrictions.

Publikationsverlauf

Eingereicht: 23. August 2022

Angenommen: 25. Juni 2023

Artikel online veröffentlicht:
28. Juli 2023

• References

• 1 Johnson D, Wilkie AO. Craniosynostosis. Eur J Hum Genet 2011; 19 (04) 369-376
• 2 Rizell S, Karlsson P, Ransjö M, Westerlund A, Yehia Z, Kölby L. Lateral and frontal cephalometric measurements in a cohort with Saethre-Chotzen syndrome. Cleft Palate Craniofac J 2021; 58 (07) 838-846
• 3 Pelc A, Mikulewicz M. Saethre-Chotzen syndrome: case report and literature review. Dent Med Probl 2018; 55 (02) 217-225
• 4 Gallagher ER, Ratisoontorn C, Cunningham ML. Saethre-Chotzen Syndrome. 2003 May 16 [Updated 2019 Jan 24]. In: Adam MP, Everman DB, Mirzaa GM. et al., Editors. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 2003. :1993-2022.
• 5 Den Ottelander BK, Van Veelen MC, De Goederen R. et al. Saethre-Chotzen syndrome: long-term outcome of a syndrome-specific management protocol. Dev Med Child Neurol 2021; 63 (01) 104-110
• 6 Junn A, Dinis J, Lu X. et al. Facial dysmorphology in Saethre-Chotzen syndrome. J Craniofac Surg 2021; 32 (08) 2660-2665
• 7 Abulezz TA, Allam KA, Wan DC, Lee JC, Kawamoto HK. Saethre-Chotzen syndrome: a report of 7 patients and review of the literature. Ann Plast Surg 2020; 85 (03) 251-255
• 8 den Ottelander B, Gaillard L, Yang S. et al. Adult Saethre-Chotzen syndrome: a unique abnormal breathing pattern. J Craniofac Surg 2021; 32 (05) e459-e461
• 9 Díez de Los Ríos Quintanero B, Gracia Rojas E, Ortiz Movilla R, Cabrejas Núñez MJ, Marín Gabriel MÁ. [Saethre-Chotzen syndrome: a case report]. Arch Argent Pediatr 2021; 119 (02) e129-e132
• 10 Takenouchi T, Sakamoto Y, Sato H. et al. Ablepharon and craniosynostosis in a patient with a localized TWIST1 basic domain substitution. Am J Med Genet A 2018; 176 (12) 2777-2780
• 11 Dollfus H, Biswas P, Kumaramanickavel G. et al. Saethre-Chotzen syndrome: notable intrafamilial phenotypic variability in a large family with Q28X TWIST mutation. Am J Med Genet 2002; 109 (03) 218-225
• 12 de Heer IM, de Klein A, van den Ouweland AM. et al. Clinical and genetic analysis of patients with Saethre-Chotzen syndrome. Plast Reconstr Surg 2005; 115 (07) 1894-1902 , discussion 1903–1905
• 13 Woods RH, Ul-Haq E, Wilkie AOM. et al. Reoperation for intracranial hypertension in TWIST1-confirmed Saethre-Chotzen syndrome: a 15-year review. Plast Reconstr Surg 2009; 123 (06) 1801-1810
• 14 Firulli BA, Krawchuk D, Centonze VE. et al. Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities. Nat Genet 2005; 37 (04) 373-381
• 15 Ratisoontorn C, Seto ML, Broughton KM, Cunningham ML. In vitro differentiation profile of osteoblasts derived from patients with Saethre-Chotzen syndrome. Bone 2005; 36 (04) 627-634
• 16 Foo R, Guo Y, McDonald-McGinn DM, Zackai EH, Whitaker LA, Bartlett SP. The natural history of patients treated for TWIST1-confirmed Saethre-Chotzen syndrome. Plast Reconstr Surg 2009; 124 (06) 2085-2095
• 17 Stoler JM, Rogers GF, Mulliken JB. The frequency of palatal anomalies in Saethre-Chotzen syndrome. Cleft Palate Craniofac J 2009; 46 (03) 280-284
• 18 Guenou H, Kaabeche K, Mée SL, Marie PJ. A role for fibroblast growth factor receptor-2 in the altered osteoblast phenotype induced by Twist haploinsufficiency in the Saethre-Chotzen syndrome. Hum Mol Genet 2005; 14 (11) 1429-1439
• 19 Peña WA, Slavotinek A, Oberoi S. Saethre-Chotzen syndrome: a case report. Cleft Palate Craniofac J 2010; 47 (03) 318-321
• 20 Lonsdale S, Yong R, Khominsky A. et al. Craniofacial abnormalities in a murine model of Saethre-Chotzen syndrome. Ann Anat 2019; 225: 33-41
• 21 Cho E, Yang TH, Shin ES, Byeon JH, Kim GH, Eun BL. Saethre–Chotzen syndrome with an atypical phenotype: identification of TWIST microdeletion by array CGH. Childs Nerv Syst 2013; 29 (11) 2101-2104
• 22 Friedman JM, Hanson JW, Graham CB, Smith DW. Saethre-Chotzen syndrome: a broad and variable pattern of skeletal malformations. J Pediatr 1977; 91 (06) 929-23
• 23 Reardon W, Winter RM. Saethre-Chotzen syndrome. J Med Genet 1994; 31 (05) 393-396
• 24 Schluth-Bolard C, Till M, Labalme A. et al. TWIST microdeletion identified by array CGH in a patient presenting Saethre-Chotzen phenotype and a complex rearrangement involving chromosomes 2 and 7. Eur J Med Genet 2008; 51 (02) 156-164
• 25 Kress W, Schropp C, Lieb G. et al. Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome. Eur J Hum Genet 2006; 14 (01) 39-48
• 26 Tahiri Y, Bastidas N, McDonald-McGinn DM. et al. New pattern of sutural synostosis associated with TWIST gene mutation and Saethre-Chotzen syndrome: peace sign synostosis. J Craniofac Surg 2015; 26 (05) 1564-1567
• 27 Zhou Y, Koelling N, Fenwick AL. et al. Disruption of TWIST1 translation by 5′ UTR variants in Saethre-Chotzen syndrome. Hum Mutat 2018; 39 (10) 1360-1365
• 28 Oram KF, Gridley T. Mutations in snail family genes enhance craniosynostosis of Twist1 haplo-insufficient mice: implications for Saethre-Chotzen syndrome. Genetics 2005; 170 (02) 971-974
• 29 Kilcoyne S, Luscombe C, Scully P. et al. Language development, hearing loss, and intracranial hypertension in children with TWIST1-confirmed Saethre-Chotzen syndrome. J Craniofac Surg 2019; 30 (05) 1506-1511
• 30 El Ghouzzi V, Lajeunie E, Le Merrer M. et al. Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome. Eur J Hum Genet 1999; 7 (01) 27-33
• 31 Hirsch N, Eshel R, Bar Yaacov R. et al. Unraveling the transcriptional regulation of TWIST1 in limb development. PLoS Genet 2018; 14 (10) e1007738
• 32 Firulli AB, Conway SJ. Phosphoregulation of Twist1 provides a mechanism of cell fate control. Curr Med Chem 2008; 15 (25) 2641-2647
• 33 Qin Q, Xu Y, He T, Qin C, Xu J. Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms. Cell Res 2012; 22 (01) 90-106
• 34 Massalska D, Bijok J, Kucińska-Chahwan A. et al. Prenatal diagnosis of craniosynostosis (compound Saethre-Chotzen syndrome phenotype) caused by a de novo complex chromosomal rearrangement (1; 4; 7) with a microdeletion of 7p21.3-7p15.3, including TWIST1 gene–a case report. Ginekol Pol 2014; 85 (07) 541-544
• 35 Connerney J, Andreeva V, Leshem Y. et al. Twist1 homodimers enhance FGF responsiveness of the cranial sutures and promote suture closure. Dev Biol 2008; 318 (02) 323-334
• 36 Connerney J, Andreeva V, Leshem Y, Muentener C, Mercado MA, Spicer DB. Twist1 dimer selection regulates cranial suture patterning and fusion. Dev Dyn 2006; 235 (05) 1345-1357
• 37 Ye X, Guilmatre A, Reva B. et al. Mutation screening of candidate genes in patients with nonsyndromic sagittal craniosynostosis. Plast Reconstr Surg 2016; 137 (03) 952-961
• 38 Richards S, Aziz N, Bale S. et al; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (05) 405-424
• 39 Miller KA, Twigg SR, McGowan SJ. et al. Diagnostic value of exome and whole genome sequencing in craniosynostosis. J Med Genet 2017; 54 (04) 260-268
• 40 Alghamdi M, Alhumsi TR, Altweijri I. et al. Clinical and Genetic characterization of craniosynostosis in Saudi Arabia. Front Pediatr 2021; 9: 582816