Osteogenesis imperfecta (OI) is a genetic disorder characterised by low bone 
mineral density resulting in fractures. 85-90% of patients with OI carry a 
variant in the type 1 collagen genes, COL1A1 and COL1A2, which follows an 
autosomal dominant pattern of inheritance. However, within the last two decades, 
there have been growing number of variants identified in genes that follow an 
autosomal recessive pattern of inheritance. Our proband is a child born in 
Mexico with multiple fractures of ribs, minimal calvarial mineralisation, 
platyspondyly, marked compression and deformed long bones. He also presented 
with significant hydranencephaly, requiring ventilatory support from birth, and 
died at 8days of age. A homozygous c.338_357delins22 variant in exon 2 of 
SERPINH1 was identified. This gene encodes heat shock protein 47, a 
collagen-specific chaperone which binds to the procollagen triple helix and is 
responsible for collagen stabilisation in the endoplasmic reticulum. There is 
minimal literature on the mechanism of action for variants in SERPINH1 resulting 
in osteogenesis imperfecta. Here we discuss this rare, previously unreported 
variant, and expand on the phenotypic presentation of this novel variant 
resulting in a severe, lethal phenotype of OI in association with 
hydranencephaly.