Osteoglophonic Dysplasia

Excerpt

Clinical characteristics: Osteoglophonic dysplasia (OGD) is characterized by multisuture craniosynostosis (including cloverleaf skull), distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth), profound short stature with rhizomelia, and short, broad hands and feet. Radiographs show copper beaten appearance to skull, multiple cystic long bone lesions consistent with non-ossifying fibromas, irregular vertebral bodies, and osteopenia with increased risk of fractures.

Diagnosis/testing: The diagnosis of OGD is established in a proband with characteristic clinical and imaging findings and a heterozygous pathogenic gain-of-function variant in FGFR1 identified by molecular genetic testing.

Management: Treatment of manifestations: Management of musculoskeletal manifestations per skeletal dysplasia or physiatry clinic; address mobility issues in those with bone deformity; early intervention such as physical therapy, occupational therapy, and speech therapy to optimize developmental outcomes; surgical repair in the first year of life in those with multisuture craniosynostosis; early initiation of topical eye lubrication in those with inadequate lid closure; jaw surgery to advance the midface; pediatric dental and orthodontic care; surgical interventions as needed for sleep apnea; treatment with phosphate as needed per endocrinologist; standard treatment of hernias per gastroenterologist/surgeon.

Surveillance: At each visit monitor growth, developmental progress, and educational needs, and assess for recurrent and pathologic fractures, incomplete eyelid closure, and manifestations of sleep apnea. Clinical evaluation of head circumference and for manifestations of increased intracranial pressure at least every three months in the first year of life. Evaluation by a craniofacial orthodontist when secondary teeth have erupted. Assess serum phosphate and serum FGF23 as recommended by endocrinologist. Monitor body temperature following sedation for procedures.

Agents/circumstances to avoid: Sports restrictions may be necessary for activities that carry a potential for head or neck injury; individuals with severe proptosis need to wear protective eyewear during activities with risk of eye injury.

Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment of developmental and craniofacial manifestations.

Genetic counseling: OGD is inherited in an autosomal dominant manner. Most individuals diagnosed with OGD represent simplex cases; some individuals diagnosed with OGD have an affected parent. Each child of an individual with OGD has a 50% chance of inheriting the FGFR1 pathogenic variant. Once the FGFR1 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible. Because many individuals with short stature have reproductive partners with short stature, offspring of individuals with OGD may be at risk of having double heterozygosity for two dominantly inherited bone growth disorders; the phenotypes of these individuals are distinct from those of the parents, and the affected individuals have serious sequelae and poor outcomes. Pregnant women carrying fetuses affected by OGD should be monitored during pregnancy for features that can affect early morbidity and mortality and should be encouraged to deliver in a hospital with ready access to a pediatric otolaryngologist, plastic surgeon, neurosurgeon, and pulmonary medicine specialist.