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Current Opinion in Pediatrics Aug 2019This review is timely given the 2018 publication of the first international Consensus Statement for the diagnosis and management of pseudohypoparathyroidism (PHP) and... (Review)
Review
PURPOSE OF REVIEW
This review is timely given the 2018 publication of the first international Consensus Statement for the diagnosis and management of pseudohypoparathyroidism (PHP) and related disorders. The purpose of this review is to provide the knowledge needed to recognize and manage PHP1A, pseudopseudohypoparathyroidism (PPHP) and PHP1B - the most common of the subtypes - with an overview of the entire spectrum and to provide a concise summary of management for clinical use. This review will draw from recent literature as well as personal experience in evaluating hundreds of children and adults with PHP.
RECENT FINDINGS
Progress is continually being made in understanding the mechanisms underlying the PHP spectrum. Every year, through clinical and laboratory studies, the phenotypes are elucidated in more detail, as are clinical issues such as short stature, brachydactyly, subcutaneous ossifications, cognitive/behavioural impairments, obesity and metabolic disturbances. Headed by a European PHP consortium, experts worldwide published the first international Consensus that provides detailed guidance in a systematic manner and will lead to exponential progress in understanding and managing these disorders.
SUMMARY
As more knowledge is gained from clinical and laboratory investigations, the mechanisms underlying the abnormalities associated with PHP are being uncovered as are improvements in management.
Topics: Adult; Animals; Child; Child, Preschool; Chromogranins; Female; GTP-Binding Protein alpha Subunits, Gs; Growth Hormone; Humans; Infant; Male; Mice; Obesity; Pseudohypoparathyroidism; Pseudopseudohypoparathyroidism
PubMed: 31145125
DOI: 10.1097/MOP.0000000000000783 -
BoneKEy Reports Nov 2012Acrodysostosis (ADO) refers to a heterogeneous group of rare skeletal dysplasia that share characteristic features including severe brachydactyly, facial dysostosis and... (Review)
Review
Acrodysostosis (ADO) refers to a heterogeneous group of rare skeletal dysplasia that share characteristic features including severe brachydactyly, facial dysostosis and nasal hypoplasia. The literature describing acrodysostosis cases has been confusing because some reported patients may have had other phenotypically related diseases presenting with Albright Hereditary Osteodystrophy (AHO) such as pseudohypoparathyroidism type 1a (PHP1a) or pseudopseudohypoparathyroidism (PPHP). A question has been whether patients display or not abnormal mineral metabolism associated with resistance to PTH and/or resistance to other hormones that bind G-protein coupled receptors (GPCR) linked to Gsα, as observed in PHP1a. The recent identification in patients affected with acrodysostosis of defects in two genes, PRKAR1A and PDE4D, both important players in the GPCR-Gsα-cAMP-PKA signaling, has helped clarify some issues regarding the heterogeneity of acrodysostosis, in particular the presence of hormonal resistance. Two different genetic and phenotypic syndromes are now identified, both with a similar bone dysplasia: ADOHR, due to PRKAR1A defects, and ADOP4 (our denomination), due to PDE4D defects. The existence of GPCR-hormone resistance is typical of the ADOHR syndrome. We review here the PRKAR1A and PDE4D gene defects and phenotypes identified in acrodysostosis syndromes, and discuss them in view of phenotypically related diseases caused by defects in the same signaling pathway.
PubMed: 24363928
DOI: 10.1038/bonekey.2012.225 -
Molecular Syndromology May 2016Bardet-Biedl syndrome (BBS) is a rare autosomal recessive genetic disorder. It is characterized by heterogeneous clinical manifestations including primary features of... (Review)
Review
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive genetic disorder. It is characterized by heterogeneous clinical manifestations including primary features of the disease (rod-cone dystrophy, polydactyly, obesity, genital abnormalities, renal defects, and learning difficulties) and secondary BBS characteristics (developmental delay, speech deficit, brachydactyly or syndactyly, dental defects, ataxia or poor coordination, olfactory deficit, diabetes mellitus, congenital heart disease, etc.); most of these symptoms may not be present at birth but appear and progressively worsen during the first and second decades of life. At least 20 BBS genes have already been identified, and all of them are involved in primary cilia functioning. Genetic diagnosis of BBS is complicated due to lack of gene-specific disease symptoms; however, it is gradually becoming more accessible with the invention of multigene sequencing technologies. Clinical management of BBS is largely limited to a symptomatic treatment. Mouse experiments demonstrate that the most debilitating complication of BBS, blindness, can be rescued by topical gene therapy. There is a published case report describing the delay of BBS symptoms by nutritional compensation of the disease-related biochemical deficiencies. Progress in DNA testing technologies is likely to rapidly resolve all limitations in BBS diagnosis; however, much slower improvement is expected with regard to BBS treatment.
PubMed: 27385962
DOI: 10.1159/000445491 -
Hand (New York, N.Y.) Dec 2016Poland anomaly is a sporadic, phenotypically variable congenital condition usually characterized by unilateral pectoral muscle agenesis and ipsilateral hand deformity.... (Review)
Review
Poland anomaly is a sporadic, phenotypically variable congenital condition usually characterized by unilateral pectoral muscle agenesis and ipsilateral hand deformity. A comprehensive review of the medical literature on Poland anomaly was performed using a Medline search. Poland anomaly is a sporadic, phenotypically variable congenital condition usually characterized by unilateral, simple syndactyly with ipsilateral limb hypoplasia and pectoralis muscle agenesis. Operative management of syndactyly in Poland anomaly is determined by the severity of hand involvement and the resulting anatomical dysfunction. Syndactyly reconstruction is recommended in all but the mildest cases because most patients with Poland anomaly have notable brachydactyly, and digital separation can improve functional length. Improved understanding the etiology and presentation of Poland anomaly can improve clinician recognition and management of this rare congenital condition.
Topics: Brachydactyly; Hand Deformities, Congenital; Humans; Pectoralis Muscles; Phenotype; Poland Syndrome; Syndactyly
PubMed: 28149203
DOI: 10.1177/1558944716647355 -
Current Opinion in Endocrinology,... Feb 2017To provide readers with a review of contemporary literature describing the evolving understanding of the pseudohypoparathyroidism type 1A (PHP1A) phenotype. (Review)
Review
PURPOSE OF REVIEW
To provide readers with a review of contemporary literature describing the evolving understanding of the pseudohypoparathyroidism type 1A (PHP1A) phenotype.
RECENT FINDINGS
The classic features of PHP1A include multihormone resistance and the Albright Hereditary Osteodystrophy phenotype (round facies, short stature, subcutaneous ossifications, brachydactyly, and early-onset obesity. Obesity may be because of a decrease in resting energy expenditure because most patients do not report significant hyperphagia. Patients with PHP1A have an increased risk of type 2 diabetes. In addition to brachydactyly and short stature, orthopedic complications can include spinal stenosis and carpal tunnel syndrome. Hearing loss, both sensorineural and conductive, has been reported in PHP1A. In addition, ear-nose-throat findings include decreased olfaction and frequent otitis media requiring tympanostomy tubes. Sleep apnea was shown to be 4.4-fold more common in children with PHP1A compared with other obese children; furthermore, asthma-like symptoms have been reported. These new findings are likely multifactorial and further research is needed to better understand these nonclassic features of PHP1A.
SUMMARY
Along with the Albright Hereditary Osteodystrophy phenotype and hormone resistance, patients with PHP1A may have additional skeletal, metabolic, ear-nose-throat, and pulmonary complications. Understanding these nonclassic features will help improve clinical care of patients with PHP1A.
Topics: Diabetes Mellitus, Type 2; Drug Resistance; Energy Metabolism; Hormones; Humans; Obesity; Phenotype; Pseudohypoparathyroidism
PubMed: 27875418
DOI: 10.1097/MED.0000000000000306