Systematic analysis of physical examination characteristics of 94 individuals with Joubert syndrome: Keys to suspecting the diagnosis

Abstract

Joubert syndrome (JS) is a neurodevelopmental disorder characterized by hypotonia and developmental delay, as well as the obligatory molar tooth sign on brain imaging. Since hypotonia and developmental delay are nonspecific features, there must be a high level of clinical suspicion of JS so that the diagnostic brain imaging and/or molecular testing for the >38 genes associated with JS is/are obtained. The goal of this study was to analyze clinical photographs of a cohort of patients with JS to define a list of physical examination features that should prompt investigation for JS. Analysis of photographs from 94 individuals with JS revealed that there is a recognizable pattern of facial features in JS that changes over time as individuals age. Macrocephaly, head tilting even when looking straight ahead, eye movement abnormalities (oculomotor apraxia, nystagmus, strabismus), and ptosis are common in those with JS. Distinctive features in younger children include triangular-shaped open mouth with tongue protrusion; in older children and adults, mandibular prognathia and prominent nasal bridge are common.

Novel compound heterozygous variants in the CSPP1 gene causes Joubert syndrome: case report and literature review of the CSPP1 gene’s pathogenic mechanism

“…Joubert syndrome is an autosomal recessive congenital disease caused by a homozygote or compound heterozygous variant. According to previous literature (18)(19)(20)(21)(22)(23), the affected children may exhibit neonatal hypotonia, abnormal eye movements, developmental delays, episodic respiratory dysregulation, progressive cerebellar ataxia development, and cognitive impairment. JS patients present with multisystem organ involvement, including fibrocystic kidney and liver disease, retinal dystrophy, chorioretinal coloboma, occipital encephalocele, and polydactyly (24).…”