A pediatric case of diphthamide biosynthesis 1 gene defect presenting with developmental delay, short stature,...

Diphthamide biosynthesis 1 is a critical component of the multiprotein complex responsible for diphthamide biosynthesis. Autosomal recessive variants in Diphthamide biosynthesis 1 gene are associated with an ultra-rare neurodevelopmental disorder called developmental delay with short stature, dysmorphic facial features, and sparse hair, also known as Loucks-Innes syndrome. To the best of our knowledge, there have been fewer than 20 reported cases of Loucks-Innes syndrome in the literature.

We present a 14-year-old Yemeni male patint with novel homozygous variants in diphthamide biosynthesis 1, who presented with a history of congenital hydrocephalus, neonatal seizures, dysmorphic face, and sparse hair. The patient also had aortic root dilation, intellectual disability, short stature, hypoplastic toenails, and mixed conductive and sensorineural hearing loss in both ears. He was only able to move around by crawling and was confined to a wheelchair.

This case report adds to the limited knowledge on developmental delay with short stature, dysmorphic facial features, and sparse hair and highlights the importance of genetic workup in patients with intellectual disability, short stature, and craniofacial and ectodermal anomalies. Further research is needed to better understand the pathogenesis and clinical features of this rare syndrome.