When the Clinical Picture Demands More: Dual Diagnosis of Neurofibromatosis Type 1 and Auriculocondylar Syndrome 2A in a Pediatric Case.

INTRODUCTION

Neurofibromatosis type 1 (NF1) and auriculocondylar syndrome 2A (ARCND2A) are distinct rare genetic disorders, each with characteristic clinical features. The simultaneous occurrence of these two syndromes is exceptionally rare and poses significant diagnostic challenges, especially in pediatric patients with complex phenotypes.

CASE PRESENTATION: We report a 3-year-old Turkish girl who presented with multiple café-au-lait macules and dysmorphic facial features. Initial single-gene sequencing revealed a variant in the NF1 gene; however, the presence of severe craniofacial anomalies prompted further investigation. Clinical exome sequencing identified a likely pathogenic PLCB4 variant, establishing a dual molecular diagnosis of NF1 and ARCND2A. Comprehensive radiological assessment, including brain and orbital MRI with temporal bone CT, and maxillo-mandibular computed cone beam tomography (CBCT), revealed both craniofacial anomalies and central nervous system lesions consistent with ARCND2A and NF1. Notable findings included dehiscence in the left superior semicircular canal, mandibular and left sphenoid wing hypoplasia, as well as NF1-related hamartomatous lesions and optic pathway involvement.

CONCLUSION

The coexistence of NF1 and ARCND2A in a single pediatric patient complicates the clinical picture due to overlapping and atypical features. This dual diagnosis highlights the importance of considering multiple genetic etiologies when clinical findings cannot be fully explained by a single disorder. This case underscores the critical role of comprehensive genomic and radiological evaluation in children with unexplained or complex presentations. Recognizing the potential for multilocus genetic diagnoses is essential for accurate diagnosis, management, and genetic counseling.