Deformations associated with arthrogryposis

Hall, Judith G.

doi:10.1002/ajmg.a.62151

Cited by 8 publications

(7 citation statements)

References 21 publications

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“…In the postnatal period, 11/13 participants (85%) showed microretrognathia, which is reported as the most striking craniofacial effect of arthrogryposis [ 30 , 31 ]. Trismus was present in 8/13 participants (61%), usually determined by a variable association of microretrognathia and narrow mouth.…”

Section: Resultsmentioning

confidence: 99%

Clinical and Genetic Findings in a Series of Eight Families with Arthrogryposis

Pollazzon

Caraffi

Faccioli

et al. 2021

Genes

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The term “arthrogryposis” is used to indicate multiple congenital contractures affecting two or more areas of the body. Arthrogryposis is the consequence of an impairment of embryofetal neuromuscular function and development. The causes of arthrogryposis are multiple, and in newborns, it is difficult to predict the molecular defect as well as the clinical evolution just based on clinical findings. We studied a consecutive series of 13 participants who had amyoplasia, distal arthrogryposis (DA), or syndromic forms of arthrogryposis with normal intellectual development and other motor abilities. The underlying pathogenic variants were identified in 11 out of 13 participants. Correlating the genotype with the clinical features indicated that prenatal findings were specific for DA; this was helpful to identify familial cases, but features were non-specific for the involved gene. Perinatal clinical findings were similar among the participants, except for amyoplasia. Dilatation of the aortic root led to the diagnosis of Loeys–Dietz syndrome (LDS) in one case. The phenotype of DA type 5D (DA5D) and Escobar syndrome became more characteristic at later ages due to more pronounced pterygia. Follow-up indicated that DA type 1 (DA1)/DA type 2B (DA2B) spectrum and LDS had a more favorable course than the other forms. Hand clenching and talipes equinovarus/rocker bottom foot showed an improvement in all participants, and adducted thumb resolved in all forms except in amyoplasia. The combination of clinical evaluation with Next Generation Sequencing (NGS) analysis in the newborn may allow for an early diagnosis and, particularly in the DAs, suggests a favorable prognosis.

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Section: Resultsmentioning

confidence: 99%

Clinical and Genetic Findings in a Series of Eight Families with Arthrogryposis

Pollazzon

Caraffi

Faccioli

et al. 2021

Genes

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“…This results in overlapping phenotypic characteristics, comprising intrauterine growth restriction, pulmonary hypoplasia, and craniofacial dysmorphic features with hypertelorism, high bridge of the nose, depressed tip of the nose, long philtrum, micrognathia, and cleft palate, in addition to generalized contractures. This set of congenital deformations is described as “fetal akinesia deformation sequence.” 2 …”

Section: Introductionmentioning

confidence: 99%

“…This set of congenital deformations is described as "fetal akinesia deformation sequence." 2 Intrinsic, or fetal etiologies of MCC, can be due to structural or functional abnormalities of the central nervous system (CNS), motor neuron dysfunction, peripheral neuropathy, neuromuscular junction (NMJ) disorders, channelopathies, muscular dystrophies, hypotonia, and connective tissue disorders. The vast majority of these fetal conditions are of genetic origin, and to date, more than 400 distinct disorders with MCC have been described.…”

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confidence: 99%

Functional loss of ubiquitin‐specific protease 14 may lead to a novel distal arthrogryposis phenotype

et al. 2022

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Multiple congenital contractures (MCC) comprise a number of rare, non‐progressive conditions displaying marked phenotypic and etiologic heterogeneity. A genetic cause can be established in approximately half of the affected individuals, attributed to genetic defects in the formation and functioning of the central and peripheral nervous system, neuromuscular junctions, skeletal muscles, and connective tissue. Ubiquitin‐specific protease 14 (USP14) encodes a major proteasome‐associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14‐deficient mice show a phenotype similar to lethal human MCC phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. We describe a new, autosomal recessive MCC phenotype in three fetuses from two different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4‐bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11, SCV002028347) in USP14, and sequencing of family members showed segregation with the phenotype. RT‐qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense‐mediated mRNA decay. We propose that herein described fetuses represent the first human phenotype of USP14 loss, with callosal anomalies and/or cortical malformations, multiple contractures, and recognizable dysmorphic facial features.

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“…Erschwerend ist in unserem Fall die Einhaltung der orthopädischen Therapie bei einem kleinen, vulnerablen Frühgeborenen. Aufgrund postnataler Komplikationen mit intermittierend lebensbedrohlicher Verschlechterung musste die orthopädische Therapie mehrfach unterbrochen werden 1 2 3 4 5 .…”

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