Hajdu-Cheney syndrome (HCS) is an inherited skeletal disorder caused by mutations in the Notch homolog
protein 2 gene (NOTCH2). Treatment of this
rare disease is challenging because there are no established guidelines worldwide. Previous case reports using
bisphosphonates,
denosumab, or
teriparatide suggested that curative treatment for HCS did not exist yet in terms of preventing the
disease progression. Therefore, the efficacy of
romosozumab for
osteoporosis in patients with HCS needs to be evaluated. Herein, we report the case of a 43-year-old woman who had progressive
acro-osteolysis and repeated fractures since the age of 29 years. Next-generation sequencing confirmed HCS with a mutation at
nucleotide 6758G>A, leading to Trp2253Ter replacement in NOTCH2.
Romosozumab treatment was initiated because she had already received
bisphosphonate for more than 10 years at other hospitals. After 1 year of
romosozumab treatment, the bone mineral density (BMD) increased by 10.2%, 6.3%, and 1.3%, with Z scores of -2.9, -1.6, and -1.2 at the lumbar spine, femoral neck, and total hip, respectively. In addition,
C-telopeptide was suppressed by 26.4% (0.121 to 0.089 ng/mL), and
procollagen type I N-terminal propeptide increased by 18.7% (25.2 to 29.9 ng/mL). This was the first report of
romosozumab treatment in patient with
osteoporosis and HCS in Korea. One year of
romosozumab treatment provided substantial gains in BMD with maintaining the last acro-osteolytic status without deteriorating, representing a possible treatment option for HCS.