Muenke syndrome

Muenke syndrome is inherited in an autosomal dominant manner. Each child of an affected individual has a 50% risk of inheriting the FGFR3 pathogenic variant. A substantial proportion of affected individuals have a de novo pathogenic variant, many of which arise on the paternally derived allele and are associated with advanced paternal age. In such cases, the parents are unaffected and the recurrence risk for future siblings is low but not zero because of the possibility of parental germline mosaicism.

Main differential diagnoses include:

• : coronal synostosis with facial asymmetry, ptosis, syndactyly of fingers 2 to 3; TWIST1
• : bicoronal synostosis with marked proptosis and midface retrusion, normal extremities; FGFR2
• : bicoronal synostosis with broad, medially deviated thumbs and great toes, brachydactyly; FGFR1, FGFR2
• : craniosynostosis with craniofacial dysmorphia and symmetric syndactyly of the hands and feet; FGFR2

• Genetic testing supports establishing the diagnosis by identifying the underlying pathogenic FGFR3 variant, clarifying the genetic aetiology and providing a basis for genetic counselling and predictive testing.
• A confirmed result supports condition-specific surveillance and management options, including audiological, developmental, neurological and ophthalmological assessment.

• Kruszka P, Rolle M, Kahle KT, Muenke M. Muenke syndrome. 2006 May 10 [updated 2023 Mar 30]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. PMID: 20301588.
• Kruszka P, Addissie YA, Yarnell CM, Hadley DW, Guillen Sacoto MJ, Platte P, et al. Muenke syndrome: an international multicenter natural history study. Am J Med Genet A. 2016;170A(4):918-929. PMID: .