P367: De novo GNAS frameshift variant with extensive intracranial calcifications and dental root resorption: Expanding the phenotypic spectrum

Counseling for this case presented challenges.The MED13 pathogenic variant did not fully explain the observed anomalies and introduced new concerns about future neurodevelopment.The limited information available about MED13-related neurodevelopmental disorder, coupled with the lack of molecular testing for Goldenhar syndrome, left the family with more questions than answers.Conclusion: This case suggests a possible expansion of the phenotype associated with MED13, as congenital anomalies are not commonly reported.In addition, this case highlights the importance of counseling for broad genomic testing in infants or children who may have an evolving phenotype.Introduction: MED13 plays an important role in regulating transcription and pathogenic variants in this gene are associated with a recently described autosomal dominant neurodevelopmental disorder.Characteristic features include developmental delays, intellectual disability, behavioral differences including autism, seizures, and abnormal brain imaging.Less commonly reported features include mild facial dysmorphism, growth and feeding difficulties, eye anomalies, conductive hearing loss, and congenital heart defects.We report a 10-month-old male with clinical features concerning for Goldenhar syndrome with a de novo pathogenic variant in MED13.Case Presentation: The patient presented with multiple congenital anomalies.Prenatally, a right sided cleft lip and palate were identified.Postnatally, cheek and pre-auricular skin appendages were noted, in addition to bilateral pneumothoraces.Initial impression was Goldenhar syndrome.Ophthalmology exam, renal ultrasound and cervical spine radiographs were normal.Echocardiogram showed a patent foramen ovale and patent ductus arteriosus.Otolaryngology evaluation showed stenotic ear canals with moderate-to-severe bilateral conductive hearing loss.At the time of outpatient evaluation in clinical genetics, repair of the cleft lip and skin appendage removal were complete.There were no concerns regarding development or behavior.Exam was notable for brachycephaly, prominent forehead, mild asymmetry of the face (right>left), single palmar creases bilaterally, and broad first toe bilaterally.