A novel mutation in the RUNX2 gene; a rare cause of enlarged fontanel

Objective Cleidocranial dysplasia(CCD) is a rare dominantly inherited autosomal bone disease that is characterized by delayed closure of fontanelles,presence of open skull sutures,hypoplastic or aplastic clavicles,super numerary teeth,delayed eruption of permanent dentition,wide pubic symphysis,short stature and a variety of other skeletal changes.However signs and symptoms can vary widely in severity,even with in the same family.Heterozygous mutations in RUNX2 gene,which encodes a transcription factor required for osteoblast differentiation is responsible for CCD. Methods We present a child with enlarged fontanel admitted with febrile seizure and diagnosed as CCD. Results A 11-month-old female who is the second child of healthy parents,was born after an uncomplicated pregnancy and an uneventful delivery was admited with febrile seizure.Her parents are non-consanguineous,family history is unremarkable.Her motor skills and development were normal.Physical examination revealed dome shaped palate,frontal bossing and enlarged anteror fontanel (12x5cm).Initial laboratory evaluation including complete blood cell count, liver and renal function test, 25OH-vitamin D vitamine and thyroid function test were all normal.The electroencephalograph,brain magnetic resonance imaging,chest radiography and Denver Development Screening Test also were normal.Whole body bone survey and three-dimensionel computed tomography were normal except for widening of sagittal suture and large anterior fontanel.WES (Whole Exome Sequencing) was performed to identfy the ethiopathogenesis in which a novel,in-silico pathogenic heterozygous c.471_472delGGinsAT (p.M157_A158delinsIS) mutation was detected in RUNX2 (NM_001024630.4) gene. Conclusion Delayed closure and enlarged anterior fontanel are very common symtoms in developing countries due to undernutrition definition of 25OH-vitamine D.However it should be kept in mind that CCD also can be present with similar findings.
Keywords: febrile seizure, enlarged , fontanel, Cleidocranial dysplasia, RUNX2