Joubert syndrome misclassified as cerebral palsy/global developmental delay: lessons from a case series

Abstract

Global developmental delay (GDD) is a frequent diagnosis in pediatric practice, often labelled idiopathic or sometimes attributed to perinatal asphyxia. However, a subset of these cases is caused by underlying genetic or metabolic disorders, some of which are treatable or have disease-modifying options. Joubert syndrome (JS), a rare ciliopathy, exemplifies such conditions that may initially masquerade as nonspecific GDD. In this case series, we evaluated four children who were initially labeled as having GDD. Two of them had a history of perinatal asphyxia. All children presented with developmental delay, ataxia, ocular abnormalities, and craniofacial dysmorphism. Neuroimaging revealed cerebellar vermis hypoplasia and the characteristic molar tooth sign (MTS) in two cases, while genetic testing identified pathogenic variants in AHI1, TMEM67 and TCTN3 genes in three patients. Systemic involvement included retinitis pigmentosa, chorioretinal colobomas, hepatic fibrosis and ventricular septal defect. Each child benefited from multidisciplinary management. This series highlights that even when perinatal asphyxia is documented, children with GDD should still undergo thorough evaluation for alternative etiologies. Early identification of such conditions enables timely intervention, targeted surveillance, family counseling, and better long-term outcomes.