Keutel syndrome: Further characterization and review

Teebi, Ahmad S.; Lambert, Deborah; Kaye, Glenn M.; Al-Fifi, S; Tewfik, Ted L.; Azouz, E. Michel

doi:10.1002/(sici)1096-8628(19980630)78:2<182::aid-ajmg18>3.0.co;2-j

Cited by 54 publications

(17 citation statements)

References 9 publications

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“…Skeleton: Since early childhood, characteristic diffuse cartilage calcification involving nose, larynx, ear helix, epiglottis, trachea, bronchial rings, and costochondral junctions (Fig ) . Stippled epiphyses possible.…”

Section: Glossarymentioning

confidence: 99%

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

Wagner

Poretti

Benson

et al. 2016

Journal of Neuroimaging

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Genetic skeletal disorders (GSDs) are a heterogeneous group characterized by an intrinsic abnormality in growth and (re-)modeling of cartilage and bone. A large subgroup of GSDs has additional involvement of other structures/organs beside the skeleton, such as the central nervous system (CNS). CNS abnormalities have an important role in long-term prognosis of children with GSDs and should consequently not be missed. Sensitive and specific identification of CNS lesions while evaluating a child with a GSD requires a detailed knowledge of the possible associated CNS abnormalities. Here, we provide a pattern-recognition approach for neuroimaging findings in GSDs guided by the obvious skeletal manifestations of GSD. In particular, we summarize which CNS findings should be ruled out with each GSD. The diseases (n = 180) are classified based on the skeletal involvement (1. abnormal metaphysis or epiphysis, 2. abnormal size/number of bones, 3. abnormal shape of bones and joints, and 4. abnormal dynamic or structural changes). For each disease, skeletal involvement was defined in accordance with Online Mendelian Inheritance in Man. Morphological CNS involvement has been described based on extensive literature search. Selected examples will be shown based on prevalence of the diseases and significance of the CNS involvement. CNS involvement is common in GSDs. A wide spectrum of morphological abnormalities is associated with GSDs. Early diagnosis of CNS involvement is important in the management of children with GSDs. This pattern-recognition approach aims to assist and guide physicians in the diagnostic work-up of CNS involvement in children with GSDs and their management.

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Section: Glossarymentioning

confidence: 99%

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

Wagner

Poretti

Benson

et al. 2016

Journal of Neuroimaging

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“…Overexpression of MGP reduces ALP activity in a model of BMP2-induced osteogenesis (Xue et al, 2006) while silencing of MGP increases ALP activity (Xue et al, 2007). In humans, a rare inherited disease, Keutel syndrome (Munroe et al, 1999; Teebi et al, 1998), characterized by abnormal calcification of cartilage and stenosis of pulmonary arteries has been linked to a defective MGP gene. Ophthalmological evaluation in several patients described decreased vision and optic nerve atrophy (Hur et al, 2005; Teebi et al, 1998).…”

Section: Matrix Gla (Mgp)mentioning

confidence: 99%

“…In humans, a rare inherited disease, Keutel syndrome (Munroe et al, 1999; Teebi et al, 1998), characterized by abnormal calcification of cartilage and stenosis of pulmonary arteries has been linked to a defective MGP gene. Ophthalmological evaluation in several patients described decreased vision and optic nerve atrophy (Hur et al, 2005; Teebi et al, 1998). However, a comprehensive TM and IOP study in Keutel patients is lacking, in part because to date only about 20 cases have been reported worldwide (Hur et al, 2005)…”

Section: Matrix Gla (Mgp)mentioning

confidence: 99%

Evidence for a calcification process in the trabecular meshwork

Borrás

Comes

2009

Experimental Eye Research

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The human trabecular meshwork (TM) expresses many genes that have been associated with physiological (bone, cartilage, teeth) and pathological (vascular systems, kidney) calcification. In particular, the TM highly expresses the inhibitor of calcification Matrix Gla (MGP) gene, which encodes a vitamin K-dependent protein that requires post-translational activation to inhibit the formation of calcium precipitates. TM cells have high activity of the activating γ-carboxylase enzyme and produce active MGP. Silencing MGP increases the activity of alkaline phosphatase (ALP), an enzyme of the matrix vesicles and marker of calcification. Overexpressing MGP reduces the ALP activity induced by bone morphogenetic 2 (BMP2), a potent inducer of calcification. In this review we gathered evidence for the existence of a mineralization process in the TM. We selected twenty regulatory calcification genes, reviewed their functions in their original tissues and looked at their relative abundance in the TM by heat maps derived from existing microarrays. Although results are not yet fully conclusive and more experiments are needed, examining TM expression in the light of the calcification literature brings up many similarities. One such parallel is the role of mechanical forces in bone induction and the high levels of mineralization inhibitors found in the constantly mechanically stressed TM. During the next few years, examination of other calcification-related regulatory genes and pathways, as well as morphological examination of knockout animals would help elucidate the relevance of a calcification process to TM overall function.

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“…The reported facial features include maxillary hypoplasia, sloping forehead, broad and depressed nasal bridge with hypoplasic alae nasi, and receding chin. Seizures, thought to be secondary to central nervous system calcifications, have been reported in three previous cases, with two of them occurring after episodes of meningitis [Keutel et al, 1972;Cormode et al, 1986;Teebi et al, 1998].…”

Section: Introductionmentioning

confidence: 99%

A novel MGP mutation in a consanguineous family: Review of the clinical and molecular characteristics of Keutel syndrome

Hur

Raymond

Kahler

et al. 2005

American J of Med Genetics Pt A

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Keutel syndrome (KS) [OMIM 245150] is a rare autosomal recessive condition, characterized by abnormal cartilage calcification. Mutations in the matrix Gla protein gene (MGP) have been previously reported in three unrelated KS families. MGP is an extracellular matrix protein that acts as a calcification inhibitor by repressing bone morphogenetic protein 2 (BMP2). Loss-of-function mutations of MGP result in abnormal calcification of the soft tissues, a cardinal feature of KS. We report the fourth MGP mutation (IVS2 + 1G > A) in a consanguineous Arab family, which results in the loss of the consensus donor splice site at the exon 2-intron 2 junction. In addition to the typical manifestations, we observed abnormalities in the white matter of the brain, optic nerve atrophy, and mid-dermal elastolysis in the affected individuals of this family. This report broadens the clinical phenotype observed in patients with KS. The effect of the IVS2 + 1G > A mutation is consistent with the previously reported loss-of-function mutations of MGP.

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Keutel syndrome: Further characterization and review

Cited by 54 publications

References 9 publications

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

Evidence for a calcification process in the trabecular meshwork

A novel MGP mutation in a consanguineous family: Review of the clinical and molecular characteristics of Keutel syndrome

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