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.

To describe the manifestations, surgical treatment, and potential complications of Hajdu-Cheney syndrome (HCS), and the management of these complications.
The clinical presentation, management and outcome of HCS with severe osteoporosis and open skull sutures is presented, together with a literature review.
A 20-year-old female with HCS underwent posterior occipitocervical fusion for symptoms of progressive basilar invagination. Because of delayed lambdoid suture closure, the stiff fusion construct lead to increased suture distraction, most notably in the upright (suture-open) position, with relief in the supine (suture-closed) position. This was successfully remedied with extension of the fusion construct anteriorly over the skull vertex to the frontal bones.
In patients with HCS and other conditions with delayed suture closure, the surgeon must be cognizant of the presence of mobility at the suture lines, and consider extending the fusion construct anteriorly over the skull vertex up to the frontal bones. Because of significant osteoporosis in these syndromes, multiple fixation points and augmentation with bone graft are important principles.

OBJECTIVE: No standard strategy exists for the management of cervical kyphotic deformity in patients with severe osteoporosis. In fact, in such subpopulation, standard algorithms commonly used in patients with normal bone mineral density may not be applicable. In this Grand Rounds, the authors present a challenging case of a patient with Hajdu-Cheney syndrome, a rare disorder of bone metabolism induced by a Notch-2 mutation, who presented with cervical kyphotic deformity and severe osteoporosis.
METHODS: A 65-year-old female patient with a previous diagnosis of Hajdu-Cheney syndrome presented with cervical myelopathy and cervical kyphotic deformity. The initial MRi demonstrated multilevel cervical canal stenosis. The CT-scan also revealed marked spondylolisthesis of C6 over C7 as well as numerous laminar and pedicle fractures, resulting in a cervical kyphosis of approximately 50 degrees.
RESULTS: The patient was submitted to 360-degree decompression and fusion of the cervical spine consisting of a staged C6 anterior corpectomy and multilevel microdiscectomies with wide opening of the posterior longitudinal ligament in order to provide a satisfactory release of anterior spinal structures, followed by 24 h of cervical halo-traction, a second anterior approach for bone graft implantation in the site of the corpectomy as well as insertion of allografts and completion of the ACDF C2-T1 and plating, and, finally, a posterior C2-T3 pedicle screw instrumentation using intra-operative CT-scan (O-arm) navigation guidance.
CONCLUSIONS: This case illustrates some intra-operative nuances as well as specific surgical recommendations for cervical deformity surgery in patients with severe osteoporosis, such as avoidance of Caspar pins for interbody distraction, use of intra-operative fluoroscopy for achievement of bicortical purchase of anterior cervical screws and placement of pedicle screws during posterior instrumentation. Moreover, such illustrative case demonstrates that, in the subpopulation of patients with severe osteoporosis, it may be possible to successfully apply cervical distraction after an isolated anterior approach with a satisfactory improvement in the cervical alignment, possibly avoiding more laborious 540-degree approaches such as the previously described back-front-back or front-back-front surgical algorithms.