Expanding the Phenotypic Spectrum of BRSK2-Related Neurodevelopmental Disorder: A Case with Bilateral Ptosis and Dysmorphic Features

We report a 13-month-old boy presenting with congenital bilateral ptosis, dysmorphic features, severe atopic dermatitis, and global developmental delay. Antenatal history was notable for increased nuchal translucency and oligohydramnios, although chorionic villus sampling and microarray analysis were normal. Birth was at 38+6 weeks following induction for suspected macrosomia, with good perinatal adaptation. Early development was delayed, with Bayley III assessment at 9 months showing performance between the 1st and 2nd centiles across all domains. Following early intervention therapies, he demonstrated notable progress: currently able to pull to stand, cruise, self-feed with cutlery, and use more than five words with expressive jargon, achieving age-appropriate developmental milestones.

On examination, he displayed multiple dysmorphic features, including frontal bossing, plagiocephaly, hypertelorism, arched eyebrows, bilateral ptosis, blunted philtrum, low-set/simple ears, short broad neck, pectus excavatum, palmar simian crease, and in-turned feet, together with generalised hypotonia and facial hypotonia. Family history revealed two full siblings with autism spectrum disorder and a mother with overlapping facial features.

Molecular genetic testing identified a *likely pathogenic frameshift variant in BRSK2, c.1737dup; p.(Pro580Alafs)**, consistent with a diagnosis of BRSK2-related neurodevelopmental disorder. BRSK2 encodes brain-specific serine/threonine-protein kinase 2, involved in neuronal development, synaptic function, and social cognition; pathogenic variants are associated with intellectual disability, autism, motor delay, and dysmorphic features.

This case expands the phenotypic spectrum of BRSK2-related disorder and emphasises the importance of considering BRSK2 in children presenting with global developmental delay, congenital ptosis, hypotonia, and dysmorphic features.