PURA syndrome in a child with severe developmental delay: a challenging diagnosis

PURA syndrome is a rare autosomal dominant condition caused by de novo pathogenic variants in PURA gene and characterized by a multisystemic phenotype that includes global neurodevelopmental delay, early hypotonia, absence of speech, feeding difficulties, hypersomnolence, epilepsy and movement disorders.

We report a 9-year-old girl with hypotonia and feeding difficulties with failure to thrive since the neonatal period. At the age of 3 years motor and intellectual delay were evident, she had a wide-based gait, no speech and an exaggerated acoustic startle response. She developed hand-mouthing stereotypies and epilepsy at 6 years old. The 24 hours continuous electroencephalogram monitoring revealed global slow activity and frequent epileptiform activity in left temporal and centrotemporal areas. The brain MRI revealed delayed myelination. At 6 years old the clinical exome sequencing identified a heterozygous pathogenic variant in the PURA gene, c.153delA p.(Leu54CysfsTer24).

PURA syndrome has clinical features similar to other neurological disorders but the association with some clinical features, not as common in other neurological entities, like never being able to speak but being able to follow simple orders and exaggerated acoustic startle response, should raise the suspicion of PURA syndrome and genetic analysis must be performed to confirm the diagnosis and provide early multidisciplinary intervention.