Osteogenesis Imperfecta Type 4 With COL1A2 c.1135G>A (p.Gly379Arg) Variant: Unmodified by Concurrent ALPL c.1559delT...

Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder primarily caused by pathogenic variants in type I collagen genes, while hypophosphatasia (HPP) is a metabolic bone disease resulting from reduced activity of tissue-nonspecific alkaline phosphatase (ALP) due to ALPL variants. We report the case of a male infant initially referred for evaluation of femoral bowing and low serum ALP, suggestive of HPP. Prenatal ultrasonography demonstrated limb shortening, and postnatal imaging confirmed femoral bowing; notably, blue sclerae were absent. Biochemical analysis showed persistently low ALP with mildly elevated urinary phosphoethanolamine. Genetic testing identified a heterozygous ALPL variant, c.1559delT (p.Leu520ArgfsTer86), a frequent allele in Japan recognized for its association with an asymptomatic carrier phenotype. Subsequent eruption of the primary tooth revealed dentinogenesis imperfecta. Further genetic evaluation demonstrated a previously reported heterozygous COL1A2 variant, c.1135G>A (p.Gly379Arg). Based on the clinical constellation of perinatal femoral deformity, dentinogenesis imperfecta, and absent blue sclerae, a diagnosis of OI, moderate form (Sillence type 4), COL1A2-related (OI type 4) was established. Although prenatal femoral bowing is a common feature of both OI and HPP, the absence of characteristic rachitic features led us to conclude that the bone abnormalities were consistent with a diagnosis of OI type 4. This case suggests that the ALPL c.1559delT carrier state may not significantly modify the phenotype of OI.