Alpha 1 antitrypsin deficiency alleles are associated with joint dislocation and scoliosis in Williams syndrome

Morris, Colleen A.; Pani, Ariel M.; Mervis, Carolyn Β.; Rios, Cecilia; Kistler, Doris J.; Gregg, Ronald G.

doi:10.1002/ajmg.c.30265

Cited by 18 publications

(18 citation statements)

References 30 publications

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“…46 Lordosis and kyphosis are common at all ages; 18% have scoliosis. 6,47 Children with WS have a unique cognitive and behavioral profile. 7,48,49 Cognitive, motor, and language delay are universal, and in 75% of children, intellectual disability is ultimately diagnosed.…”

Section: Neurology Development Cognition and Behaviormentioning

confidence: 99%

Health Care Supervision for Children With Williams Syndrome

Morris

Braddock

2020

Pediatrics

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This set of recommendations is designed to assist the pediatrician in caring for children with Williams syndrome (WS) who were diagnosed by using clinical features and with chromosome 7 microdeletion confirmed by fluorescence in situ hybridization, chromosome microarray, or multiplex ligation-dependent probe amplification. The recommendations in this report reflect review of the current literature, including previously peer-reviewed and published management suggestions for WS, as well as the consensus of physicians and psychologists with expertise in the care of individuals with WS. These general recommendations for the syndrome do not replace individualized medical assessment and treatment. Williams syndrome (WS), also known as Williams-Beuren syndrome, is caused by a deletion of part of chromosome 7 and is a multisystem disorder that was first identified as a distinct clinical entity in 1961. 1 It is present at birth with a prevalence of 1 in 7500 2 and affects boys and girls equally. Children with WS usually come to the attention of pediatricians during infancy or early childhood. WS is characterized by dysmorphic facies (100%), cardiovascular disease (80%; most commonly supravalvular aortic stenosis [SVAS]), intellectual disability (75%), a characteristic cognitive profile (90%), and idiopathic hypercalcemia (15% to 45%). 1,3-7 The deleted portion of chromosome 7q11.23 seen in WS is 1.5 to 1.8 Mb and contains 26 to 28 genes. 3,4,8 It includes the ELN gene that codes for the structural protein elastin, which is an important component of the elastic fibers found in the connective tissue of many organs. The ELN deletion explains some of the characteristics of WS, such as some of the facial features, hoarse voice, inguinal hernia, bladder and bowel diverticula, cardiovascular disease, and orthopedic problems. The pathogenesis of other characteristics, such as intellectual disability, is likely attributable to deletion of contiguous genes in the region. Most deletions in the WS region are de novo. Affected individuals have a 50% chance of transmitting the deletion to offspring. A specific inversion

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Section: Neurology Development Cognition and Behaviormentioning

confidence: 99%

Health Care Supervision for Children With Williams Syndrome

Morris

Braddock

2020

Pediatrics

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“…Hypotonia may impact infant feeding, as low tone in the facial musculature can weaken suckling (Taeusch et al, ). Persistent joint laxity may contribute to the infrequent reports of joint dislocation in the WS population (up to 2%; Morris et al, ).…”

Section: Overview and Literature Review Of Musculoskeletal Features Imentioning

confidence: 99%

Description of common musculoskeletal findings in Williams Syndrome and implications for therapies

2016

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Williams syndrome (WS), also referred to as Williams-Beuren syndrome (WBS), is a relatively rare genetic disorder affecting ∼1/10,000 persons. Since the disorder is caused by a micro-deletion of ∼1.5 Mb, it is not surprising that the manifestations of WS are extremely broad, involving most body systems. In this paper, we primarily focus on the musculoskeletal aspects of WS as these findings have not been the subject of a comprehensive review. We review the MSK features commonly seen in individuals with WS, along with related sensory and neurological issues interacting with and compounding underlying MSK abnormalities. We end by providing perspective, particularly from the vantage point of a physical therapist, on therapeutic interventions to address the most common MSK and related features seen in WS. Clin. Anat. 29:578-589, 2016. © 2016 Wiley Periodicals, Inc.

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“…Contractures may also develop in patients with elastic fiber disorders. 6,8,72 Large joints are typically affected, but the involvement of the small joints of the hand have been described as well. 6 Contractures often develop during childhood; some may remain stable while others will worsen in severity with age.…”

Section: Contracturesmentioning

confidence: 99%

“…6 Contractures often develop during childhood; some may remain stable while others will worsen in severity with age. 6,72 Although the impact can be mild for some patients, others struggle with gait abnormalities, general coordination, and simple daily activities such as dressing and feeding. These limitations, along with cosmetic concerns, can have a significant psychosocial impact.…”

Section: Contracturesmentioning

confidence: 99%

Elastic fibers in orthopedics: Form and function in tendons and ligaments, clinical implications, and future directions

Hill

Eekhoff

Brophy

et al. 2020

Journal Orthopaedic Research

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Elastic fibers are an essential component of the extracellular matrix of connective tissues. The focus of both clinical management and scientific investigation of elastic fiber disorders has centered on the cardiovascular manifestations due to their significant impact on morbidity and mortality. As such, the current understanding of the orthopedic conditions experienced by these patients is limited. The musculoskeletal implications of more subtle elastic fiber abnormalities, whether due to allelic variants or age-related tissue degeneration, are also not well understood. Recent advances have begun to uncover the effects of elastic fiber deficiency on tendon and ligament biomechanics; future research must further elucidate mechanisms governing the role of elastic fibers in these tissues. The identification of population-based genetic variations in elastic fibers will also be essential. Minoxidil administration, modulation of protein expression with micro-RNA molecules, and direct injection of recombinant elastic fiber precursors have demonstrated promise for therapeutic intervention, but further work is required prior to consideration for orthopedic clinical application. This review provides an overview of the role of elastic fibers in musculoskeletal tissue, summarizes current knowledge of the orthopedic manifestations of elastic fiber abnormalities, and identifies opportunities for future investigation and clinical application.

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Alpha 1 antitrypsin deficiency alleles are associated with joint dislocation and scoliosis in Williams syndrome

Cited by 18 publications

References 30 publications

Health Care Supervision for Children With Williams Syndrome

Health Care Supervision for Children With Williams Syndrome

Description of common musculoskeletal findings in Williams Syndrome and implications for therapies

Elastic fibers in orthopedics: Form and function in tendons and ligaments, clinical implications, and future directions

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