Context: X-linked Hypophosphatemic Rickets (XLH) is characterized by hypophosphataemia and growth retardation. Early diagnosis and treatment improve growth.

Objective: To describe long-term observations of a family with XLH due to a novel mutation of the PHEX gene with unusual clinical features, including normal growth.

Patients: The mother and her two sons were followed in the same institution for nearly 30 years.

Results: The mother had hypophosphatemia and normal height (Z score: -0.6) without ever receiving any treatment. Her two sons achieved final heights of 183.7 cm (Z score: -0.01) and 182.7 cm (Z score:-0.18), respectively, despite late initiation of treatment with phosphate and low serum phosphate levels. In addition, they had reversible proximal myopathy which took about 7 years to resolve in one of them. Direct sequencing of the PHEX gene revealed a new splice site mutation in intron 4 of the gene (IVS4+6T>C) resulting in skipping of exon 4.

Conclusions: Three members of a family with XLH due to a novel mutation of the PHEX gene had a normal growth pattern despite late diagnosis and treatment of the two boys and no treatment at all of their mother. The pathophysiological basis of this phenotype-genotype association warrants further investigation.