Research genetic causes of craniosynostosis

De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder.

Reijnders MRF, Miller KA, Alvi Mohsan, Goos JAC, Lees MM, de Burca A, Henderson A. Kraus A, Mikat B, de Vries BBA, Isidor B, Kerr B, Marcelis C, Schluth-Bolard C, Deshpane C, Ruivenkamp CAL, Wieczorek D, The DDD Study, Baralle D, Blair EM, Engels H, Ludecke HJ, Eason J, Santen GWE, Clayton-Smith J, Chandler K, Tatton-Brown K, Payne K, Helbig K, Radtke K, Nugent KM, Cremer K, Strom TM, Bird LM, Sinnema M, Bitner-Glindzicz M, van Dooren MF, Alders M, Koopmans M, Brick L, Kozenko M, Harline ML, Klaassend M, Steinraths M, Cooper NS, Edery P, Yap P, Terhal PA, van der Spek PJ, Lakeman P, Taylor RL, Littlejohn RO, Pfundt R, Mercimek-ndrews S, Stegmann APA, Kant SG, McLean S, Joss S, Swagemakers SMA, Douzgou S, Wall SA, Kury S, Calpena E, Koelling N, McGowan SJ, Twigg SRF, Mathijssen IMJ, Nellaker C, Brunner HG, Wilkie AOM.

38 individuals and 2 of there mothers are described in whom a change in the TLK2 gene is found that caused consistent features: mild delay in development, behavioral disorders, gastro-intestinal problems, anomalies of the eyelids, a broad nasal tip, and a thin upper lip. The patients were treated at 26 different center in 7 different countries. Only four patients (11%) were diagnosed with craniosynostosis (metopic synostosis; bicoronal synostosis;unicoronal and sagittal synostosis; unicoronal and metopic synostosis).  TLK2 mutations are thus a rare cause for craniosynostosis.


Clinical genetics of craniosynostosis.

Wilkie AOM, Johnson D, Wall SA.

Curr Opin Pediatr. 2017 Dec;29(6):622-628

This review demonstrated how new research methods in genetics ("next-generation sequencing") have impacted the clinical genetic evaluation of craniosynostosis. A genetic cause of craniosynostosis can be found in 25% of cases. Relatively new genes that are involved in craniosynostosis have a substantial contribution: TCF12, ERF, CDC45, SMO and SMAD6.