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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 -
Human Mutation Jul 2022Different pathogenic variants in the fibrillin-1 gene (FBN1) cause Marfan syndrome and acromelic dysplasias. Whereas the musculoskeletal features of Marfan syndrome... (Review)
Review
Different pathogenic variants in the fibrillin-1 gene (FBN1) cause Marfan syndrome and acromelic dysplasias. Whereas the musculoskeletal features of Marfan syndrome involve tall stature, arachnodactyly, joint hypermobility, and muscle hypoplasia, acromelic dysplasia patients present with short stature, brachydactyly, stiff joints, and hypermuscularity. Similarly, pathogenic variants in the fibrillin-2 gene (FBN2) cause either a Marfanoid congenital contractural arachnodactyly or a FBN2-related acromelic dysplasia that most prominently presents with brachydactyly. The phenotypic and molecular resemblances between both the FBN1 and FBN2-related disorders suggest that reciprocal pathomechanistic lessons can be learned. In this review, we provide an updated overview and comparison of the phenotypic and mutational spectra of both the "tall" and "short" fibrillinopathies. The future parallel functional study of both FBN1/2-related disorders will reveal new insights into how pathogenic fibrillin variants differently affect the fibrillin microfibril network and/or growth factor homeostasis in clinically opposite syndromes. This knowledge may eventually be translated into new therapeutic approaches by targeting or modulating the fibrillin microfibril network and/or the signaling pathways under its control.
Topics: Brachydactyly; Fibrillin-1; Fibrillin-2; Humans; Marfan Syndrome; Musculoskeletal Abnormalities; Phenotype
PubMed: 35419902
DOI: 10.1002/humu.24383