Kristen S Pan

National Institutes of Health | NIH · Skeletal Diseases and Mineral Homeostasis Section

Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by germline heterozygous PTHR1 variants resulting in constitutive activation of parathyroid hormone type 1 receptor. A description of ocular manifestations of the disease is lacking. Six patients with JMC underwent a detailed ophthalmic evaluation, spectral-domain optical co...

Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of GNAS encoding for Gαs and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gαs activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed c...

Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants in GNAS, encoding for Gαs, which leads to excessive cAMP signaling in bone marrow stromal cells (BMSCs). Despite advancements in our understanding of FD pathophysiology, the effect of Gαs activation in the BMSC transcriptome remains unclear, as well as how th...

Fibrous dysplasia (FD) is a rare, disabling skeletal disease for which there are no established treatments. Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand (RANKL) as a potential treatment strategy. In this study, we investigated the mechanisms underlying RANKL inhibition in FD tissue an...

Fibrous dysplasia (FD) is characterized by expansile fibro-osseous lesions that may occur in association with endocrinopathies as part of McCune-Albright syndrome (MAS). Craniofacial FD is a significant source of morbidity, and most commonly involves the gnathic bones. There is a critical need to understand the natural history and risk factors for...

Fibrous dysplasia (FD) is a rare, disabling skeletal disease with no established treatments. Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear Kappa-B ligand (RANKL) as a potential treatment strategy. In this study, we investigated mechanisms underlying RANKL neutralization with the monoclonal antibody d...

BACKGROUND: Fibrous dysplasia (FD) is a rare, disabling disease with no established treatments. Growing evidence supports inhibiting the pro-osteoclastic factor receptor activator of nuclear Kappa-B ligand (RANKL) as a potential treatment strategy. We conducted a phase 2 trial evaluating the anti-RANKL drug denosumab in adults with FD, with an emph...

The low-density lipoprotein receptor-related protein 5 gene (LRP5), which encodes a coreceptor within the canonical Wnt signaling pathway, plays a crucial role in bone mass regulation and has been associated with several bone disorders. Autosomal dominant osteopetrosis type I (ADO type I, OMIM 607634) is a rare disease caused by heterozygous, gain-...

Background: Fibrous dysplasia (FD) is an uncommon bone disease characterized by the replacement of normal bone architecture with abnormal fibro-osseous connective tissue. Here, we discuss 2 cases of craniofacial FD, with malignant sarcomatous degeneration - a rare and morbid complication of the disease. Case history: Two cases of craniofacial FD...

This article reports quantitative measurements of intracranial volume, optic canal area, and peripapillary retinal nerve fiber layer (RNFL) for a cohort of 124 patients with craniofacial fibrous dysplasia/McCune-Albright Syndrome (FD/MAS), previously used to determine risks for developing optic disc edema [1]. Of these, 7 subjects were diagnosed wi...

Fibrous dysplasia (FD) is a mosaic skeletal disorder in which the craniofacial bones are commonly affected. Normal structures are replaced by expansile, highly vascular, fibro-osseous tissue. The typical clinical course is a gradual, asymptomatic expansion of the osseous structures. However, in the periorbital region, even minor structural changes...

Children with minor ear malformations including periauricular vestiges often undergo renal ultrasonography (RUS) to exclude renal anomalies associated with genetic conditions. The aim of this study is to assess the association between isolated periauricular vestiges and renal anomalies and delineate the indication for RUS in screening for renal ano...

Purpose of Review This review summarizes current understanding of the role of denosumab, an inhibitor of receptor activator of nuclear kappa-B ligand (RANKL), in the management of 3 skeletal neoplasms: giant cell tumors, aneurysmal bone cysts, and fibrous dysplasia. Recent Findings A growing body of literature supports denosumab use in giant cell...

Purpose: Generalized arterial calcification of infancy (GACI), characterized by vascular calcifications that are often fatal shortly after birth, is usually caused by deficiency of ENPP1. A small fraction of GACI cases result from deficiency of ABCC6, a membrane transporter. The natural history of GACI survivors has not been established in a prosp...

Background: Fibrous dysplasia (FD) is a rare disorder of expansile fibro-osseous lesions that may be associated with extraskeletal features as part of McCune-Albright syndrome (MAS). Optic disc edema is a potentially serious ophthalmologic finding that has been rarely reported in patients with FD/MAS. The purpose of this study was to investigate t...

Fibrous dysplasia (FD) is a benign bone disease characterized by expansile lesions that typically stabilize with age. Rarely, FD can undergo malignant transformation, presenting with atypical, rapid growth and destruction of adjacent bone. Other potential causes of rapid FD expansion include secondary lesions, such as aneurysmal bone cysts. We desc...

Optic neuropathy (ON) is a highly disabling complication of fibrous dysplasia (FD). The optimal test for identifying and monitoring ON in FD is unknown. Optical coherence tomography (OCT) is an imaging modality that detects retinal nerve fiber layer (RNFL) thinning, a sign of optic nerve atrophy. The purpose of this study was to 1) assess the abili...

Background: Fibrous Dysplasia (FD) is a mosaic disorder that involves fibro-osseous lesions in bone. In the presence of coexisting extra-skeletal features, it is termed McCune-Albright Syndrome (MAS). Optic disc edema (ODE) is a potentially serious finding that may progress to optic disc ischemia and nerve atrophy. We sought to determine the preval...

McCune-Albright syndrome (MAS) is a rare, mosaic disorder presenting along a broad clinical spectrum. Disease arises from somatic-activating GNAS mutations, leading to constitutive Gαs activation and ligand-independent signaling of the Gαs-coupled protein receptor. The phenotype is largely determined by location and extent of tissues in which the G...

GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in GLB1 encoding a lysosomal β-galactosidase. This disease is a continuum from the severe infantile form with rapid neurological decline to the chronic adult form, which is not life-limiting. The intermediate or type 2 form can be further classified into late infantile and juven...

Significant disfigurement and dysfunction is caused by hypertrophic scarring, a prevalent complication of burn wounds. A lack of objective tools in the assessment of scar parameters makes evaluation of scar treatment modalities difficult. 3D stereophotogrammetry, obtaining measurements from 3D photographs, represents a method to quantitate scar vol...

Fibrous dysplasia (FD) is a mosaic disease in which bone is replaced with fibro‐osseous tissue. Lesions expand during childhood, reaching final burden by age 15 years. In vitro data suggest that disease activity decreases in adulthood; however, there is no clinical data to support this concept. Bone turnover markers (BTMs) have been used as markers...

Fibrous dysplasia of bone (FD) is a mosaic disease caused by mutations in GNAS. Constitutive activation of the α‐subunit of the Gs stimulatory protein (Gαs) leads to dysregulated proliferation of bone marrow stromal cells (BMSCs), generating expansile lesions of fibrotic tissue and abnormal bone. Local bone remodeling regulation by BMSCs is also al...

Fibrous dysplasia (FD) is a mosaic disorder of benign fibro‐osseous lesions, which may be associated with extraskeletal features as part of McCune‐Albright syndrome (MAS). Cranial base abnormalities, including Chiari I malformation (CM1), in which the cerebellum extends below the foramen magnum, and secondary basilar invagination (BI), in which the...

Introduction Significant disfigurement and dysfunction is caused by hypertrophic scarring, a prevalent complication of burn wounds. The time course of hypertrophic scarring and effectiveness of scar treatment modalities have been difficult to objectively evaluate efficiently. Qualitative scar scales are intuitive and time-efficient, but lack adequa...

Defects of the nasal complex can cause significant functional and psychosocial impairment. Nasal reconstruction aims to restore the normal trilaminar structure of the nose, which includes the internal lining, cartilaginous framework, and soft tissue envelope. Among the nasal subunits, the columella is especially challenging to reconstruct due to it...