11 research outputs found
Rare Bone Diseases and Their Dental, Oral, and Craniofacial Manifestations
Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease
Pituitary stalk lesion in a 13-year-old female
Germinomas presenting with a pituitary stalk lesion and
panhypopituitarism are rare in children, and their definite diagnosis is
challenging. An invasive diagnostic approach, such as a transsphenoidal
biopsy, is often required prior to establishing a treatment regimen. A
13-year-old female presented with 1 year of secondary amenorrhea,
fatigue, and progressive thirst with polyuria. Laboratory work-up
revealed panhypopituitarism (central hypothyroidism, hypogonadotropic
hypogonadism, adrenal insufficiency and central diabetes insipidus).
alpha-Fetoprotein and beta-human chorionic gonadotropin were not
elevated in serum nor in cerebrospinal fluid. The magnetic resonance
imaging (MRI) of the pituitary region showed an enhancing infundibular
lesion, extending into the hypothalamus, and infiltrating the pituitary
gland. A transsphenoidal biopsy of the infundibular lesion confirmed the
diagnosis of germinoma (germ-cell tumor). After appropriate hormone
replacement therapy, chemotherapy and low-dose radiation therapy, the
patient achieved complete resolution of the pituitary stalk lesion on
the MRI
Clinical and genetic analysis of idiopathic normophosphatemic tumoral calcinosis in 19 patients
Age at Pubertal Development in a Hispanic-Latina Female Population: Should the Definitions Be Revisited?
The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases
The Ca2+-sensing receptor (CaSR) is a dimeric family C G protein-coupled receptor that is expressed in calcitropic tissues such as the parathyroid glands and the kidneys and signals via G proteins and β-arrestin. The CaSR has a pivotal role in bone and mineral metabolism, as it regulates parathyroid hormone secretion, urinary Ca2+ excretion, skeletal development and lactation. The importance of the CaSR for these calcitropic processes is highlighted by loss-of-function and gain-of-function CaSR mutations that cause familial hypocalciuric hypercalcaemia and autosomal dominant hypocalcaemia, respectively, and also by the fact that alterations in parathyroid CaSR expression contribute to the pathogenesis of primary and secondary hyperparathyroidism. Moreover, the CaSR is an established therapeutic target for hyperparathyroid disorders. The CaSR is also expressed in organs not involved in Ca2+ homeostasis: it has noncalcitropic roles in lung and neuronal development, vascular tone, gastrointestinal nutrient sensing, wound healing and secretion of insulin and enteroendocrine hormones. Furthermore, the abnormal expression or function of the CaSR is implicated in cardiovascular and neurological diseases, as well as in asthma, and the CaSR is reported to protect against colorectal cancer and neuroblastoma but increase the malignant potential of prostate and breast cancers