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Orphanet Journal of Rare Diseases Jan 2019Achondroplasia is the most common of the skeletal dysplasias that result in marked short stature (dwarfism). Although its clinical and radiologic phenotype has been... (Review)
Review
Achondroplasia is the most common of the skeletal dysplasias that result in marked short stature (dwarfism). Although its clinical and radiologic phenotype has been described for more than 50 years, there is still a great deal to be learned about the medical issues that arise secondary to this diagnosis, the manner in which these are best diagnosed and addressed, and whether preventive strategies can ameliorate the problems that can compromise the health and well being of affected individuals. This review provides both an updated discussion of the care needs of those with achondroplasia and an exploration of the limits of evidence that is available regarding care recommendations, controversies that are currently present, and the many areas of ignorance that remain.
Topics: Achondroplasia; Bone Diseases, Developmental; Humans; Receptor, Fibroblast Growth Factor, Type 3
PubMed: 30606190
DOI: 10.1186/s13023-018-0972-6 -
Advances in Clinical and Experimental... Jun 2021Skeletal dysplasias are a heterogeneous group of congenital bone and cartilage disorders with a genetic etiology. The current classification of skeletal dysplasias... (Review)
Review
Skeletal dysplasias are a heterogeneous group of congenital bone and cartilage disorders with a genetic etiology. The current classification of skeletal dysplasias distinguishes 461 diseases in 42 groups. The incidence of all skeletal dysplasias is more than 1 in every 5000 newborns. The type of dysplasia and associated abnormalities affect the lethality, survival and long-term prognosis of skeletal dysplasias. It is crucial to distinguish skeletal dysplasias and correctly diagnose the disease to establish the prognosis and achieve better management. It is possible to use prenatal ultrasonography to observe predictors of lethality, such as a bell-shaped thorax, short ribs, severe femoral shortening, and decreased lung volume. Individual lethal or life-limiting dysplasias may have more or less specific features on prenatal ultrasound. The prenatal features of the most common skeletal dysplasias, such as thanatophoric dysplasia, osteogenesis imperfecta type II, achondrogenesis, and campomelic dysplasia, are discussed in this article. Less frequent dysplasias, such as asphyxiating thoracic dystrophy, fibrochondrogenesis, atelosteogenesis, and homozygous achondroplasia, are also discussed.
Topics: Female; Humans; Infant, Newborn; Osteochondrodysplasias; Osteogenesis Imperfecta; Pregnancy; Receptor, Fibroblast Growth Factor, Type 3; Thanatophoric Dysplasia; Ultrasonography, Prenatal
PubMed: 34019743
DOI: 10.17219/acem/134166 -
Hormone Research in Paediatrics 2019McCune-Albright syndrome (MAS) is a rare, mosaic disorder presenting along a broad clinical spectrum. Disease arises from somatic-activating GNAS mutations, leading to... (Review)
Review
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 GNAS mutation is expressed, as well as the pathophysiologic effects of Gαs activation within these tissues. Patients pre-sent clinically with a variable combination of fibrous dysplasia of bone (FD), café-au-lait skin macules, and hyperfunctioning endocrinopathies. In bone, Gαs leads to impaired differentiation of skeletal stem cells and formation of discrete, expansile FD lesions, resulting in fractures, pain, and functional impairment. A systematic approach to diagnosis and management is critically important to optimize outcomes for patients with FD/MAS. There are no medical therapies capable of altering the disease course in FD; however, screening and treatment for endocrinopathies can mitigate some skeletal morbidities. This review summarizes current understanding of MAS pathophysiology, describes the spectrum of clinical features, and includes a detailed discussion of the recommended approach to diagnosis and management.
Topics: Chromogranins; Fibrous Dysplasia, Polyostotic; GTP-Binding Protein alpha Subunits, Gs; Humans; Mutation
PubMed: 31865341
DOI: 10.1159/000504802 -
Endocrine Reviews Apr 2020Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare disorder of striking complexity. It arises from somatic, gain-of-function mutations in GNAS, leading to... (Review)
Review
Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare disorder of striking complexity. It arises from somatic, gain-of-function mutations in GNAS, leading to mosaic Gα s activation and inappropriate production of intracellular cyclic adenosine monophosphate (cAMP). The clinical phenotype is largely determined by the location and extent of affected tissues, and the pathophysiological effects of Gα s activation within these tissues. In bone, Gα s activation results in impaired differentiation of skeletal stem cells, leading to discrete skeletal lesions prone to fracture, deformity, and pain. Extraskeletal manifestations include a variable combination of hyperpigmented macules and hyperfunctioning endocrinopathies. Distinctive age-related changes in disease development has key effects on histologic, radiographic, and clinical features. FD/MAS thus presents along a uniquely broad clinical spectrum, and the resulting challenges in diagnosis and management can be difficult for clinicians. This review presents FD/MAS in the context of a mosaic disorder of Gα s activation, providing an intellectual framework within which to understand, evaluate, and treat this interesting disease. It includes a comprehensive summary of current understanding of FD/MAS pathogenesis, and a detailed discussion of clinical presentation and management. Critical areas of unmet need are highlighted, including discussion of key challenges and potential solutions to advance research and clinical care in FD/MAS.
Topics: Fibrous Dysplasia, Polyostotic; GTP-Binding Protein alpha Subunits; Humans; Mosaicism
PubMed: 31673695
DOI: 10.1210/endrev/bnz011 -
Clinics in Perinatology Jun 2015The skeletal dysplasias are a group of more than 450 heritable disorders of bone. They frequently present in the newborn period with disproportion, radiographic... (Review)
Review
The skeletal dysplasias are a group of more than 450 heritable disorders of bone. They frequently present in the newborn period with disproportion, radiographic abnormalities, and occasionally other organ system abnormalities. For improved clinical care, it is important to determine a precise diagnosis to aid in management, familial recurrence, and identify those disorders highly associated with mortality. Long-term management of these disorders is predicated on an understanding of the associated skeletal system abnormalities, and these children are best served by a team approach to health care surveillance.
Topics: Bone Diseases, Developmental; Genetic Testing; Global Health; Humans; Infant, Newborn; Morbidity
PubMed: 26042906
DOI: 10.1016/j.clp.2015.03.003