A clinical scoring system for congenital contractural arachnodactyly

Ilse Meerschaut; Shana De Coninck; Wouter Steyaert; Angela Barnicoat; Allan Bayat; Francesco Benedicenti; Siren Berland; Edward M Blair; Jeroen Breckpot; Anna de Burca; Anne Destrée; Sixto García-Miñaúr; Andrew J Green; Bernadette C Hanna; Kathelijn Keymolen; Marije Koopmans; Damien Lederer; Melissa Lees; Cheryl Longman; Sally Ann Lynch; Alison M Male; Fiona McKenzie; Isabelle Migeotte; Ercan Mihci; Banu Nur; Florence Petit; Juliette Piard; Frank S Plasschaert; Anita Rauch; Pascale Ribaï; Iratxe Salcedo Pacheco; Franco Stanzial; Irene Stolte-Dijkstra; Irene Valenzuela; Vinod Varghese; Pradeep C Vasudevan; Emma Wakeling; Carina Wallgren-Pettersson; Paul Coucke; Anne De Paepe; Daniël De Wolf; Sofie Symoens; Bert Callewaert

doi:10.1038/s41436-019-0609-8

A clinical scoring system for congenital contractural arachnodactyly

Ilse Meerschaut, Shana De Coninck, Wouter Steyaert, Angela Barnicoat, Allan Bayat, Francesco Benedicenti, Siren Berland, Edward M Blair, Jeroen Breckpot, Anna de Burca, Anne Destrée, Sixto García-Miñaúr, Andrew J Green, Bernadette C Hanna, Kathelijn Keymolen, Marije Koopmans, Damien Lederer, Melissa Lees, Cheryl Longman, Sally Ann LynchAlison M Male, Fiona McKenzie, Isabelle Migeotte, Ercan Mihci, Banu Nur, Florence Petit, Juliette Piard, Frank S Plasschaert, Anita Rauch, Pascale Ribaï, Iratxe Salcedo Pacheco, Franco Stanzial, Irene Stolte-Dijkstra, Irene Valenzuela, Vinod Varghese, Pradeep C Vasudevan, Emma Wakeling, Carina Wallgren-Pettersson, Paul Coucke, Anne De Paepe, Daniël De Wolf, Sofie Symoens, Bert Callewaert^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Artikel › Forskning › peer review

Abstract

PURPOSE: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder manifesting joint contractures, arachnodactyly, crumpled ears, and kyphoscoliosis as main features. Due to its rarity, rather aspecific clinical presentation, and overlap with other conditions including Marfan syndrome, the diagnosis is challenging, but important for prognosis and clinical management. CCA is caused by pathogenic variants in FBN2, encoding fibrillin-2, but locus heterogeneity has been suggested. We designed a clinical scoring system and diagnostic criteria to support the diagnostic process and guide molecular genetic testing.

METHODS: In this retrospective study, we assessed 167 probands referred for FBN2 analysis and classified them into a FBN2-positive (n = 44) and FBN2-negative group (n = 123) following molecular analysis. We developed a 20-point weighted clinical scoring system based on the prevalence of ten main clinical characteristics of CCA in both groups.

RESULTS: The total score was significantly different between the groups (P < 0.001) and was indicative for classifying patients into unlikely CCA (total score <7) and likely CCA (total score ≥7) groups.

CONCLUSIONS: Our clinical score is helpful for clinical guidance for patients suspected to have CCA, and provides a quantitative tool for phenotyping in research settings.

Originalsprog	Engelsk
Sider (fra-til)	124-131
Antal sider	8
Tidsskrift	Genetics in Medicine
Vol/bind	22
Udgave nummer	1
DOI	https://doi.org/10.1038/s41436-019-0609-8
Status	Udgivet - jan. 2020
Udgivet eksternt	Ja

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10.1038/s41436-019-0609-8

Citationsformater

Meerschaut, I., De Coninck, S., Steyaert, W., Barnicoat, A., Bayat, A., Benedicenti, F., Berland, S., Blair, E. M., Breckpot, J., de Burca, A., Destrée, A., García-Miñaúr, S., Green, A. J., Hanna, B. C., Keymolen, K., Koopmans, M., Lederer, D., Lees, M., Longman, C., ... Callewaert, B. (2020). A clinical scoring system for congenital contractural arachnodactyly. Genetics in Medicine, 22(1), 124-131. https://doi.org/10.1038/s41436-019-0609-8

@article{3d1a19edf0534f0b9c5cf5cb5458b567,

title = "A clinical scoring system for congenital contractural arachnodactyly",

abstract = "PURPOSE: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder manifesting joint contractures, arachnodactyly, crumpled ears, and kyphoscoliosis as main features. Due to its rarity, rather aspecific clinical presentation, and overlap with other conditions including Marfan syndrome, the diagnosis is challenging, but important for prognosis and clinical management. CCA is caused by pathogenic variants in FBN2, encoding fibrillin-2, but locus heterogeneity has been suggested. We designed a clinical scoring system and diagnostic criteria to support the diagnostic process and guide molecular genetic testing.METHODS: In this retrospective study, we assessed 167 probands referred for FBN2 analysis and classified them into a FBN2-positive (n = 44) and FBN2-negative group (n = 123) following molecular analysis. We developed a 20-point weighted clinical scoring system based on the prevalence of ten main clinical characteristics of CCA in both groups.RESULTS: The total score was significantly different between the groups (P < 0.001) and was indicative for classifying patients into unlikely CCA (total score <7) and likely CCA (total score ≥7) groups.CONCLUSIONS: Our clinical score is helpful for clinical guidance for patients suspected to have CCA, and provides a quantitative tool for phenotyping in research settings.",

keywords = "Arachnodactyly/diagnosis, Child, Contracture/diagnosis, Diagnosis, Differential, Early Diagnosis, Female, Fibrillin-2/genetics, Genetic Testing, Humans, Male, Marfan Syndrome/diagnosis, Phenotype, Retrospective Studies, Sensitivity and Specificity, Sequence Analysis, DNA/methods",

author = "Ilse Meerschaut and {De Coninck}, Shana and Wouter Steyaert and Angela Barnicoat and Allan Bayat and Francesco Benedicenti and Siren Berland and Blair, {Edward M} and Jeroen Breckpot and {de Burca}, Anna and Anne Destr{\'e}e and Sixto Garc{\'i}a-Mi{\~n}a{\'u}r and Green, {Andrew J} and Hanna, {Bernadette C} and Kathelijn Keymolen and Marije Koopmans and Damien Lederer and Melissa Lees and Cheryl Longman and Lynch, {Sally Ann} and Male, {Alison M} and Fiona McKenzie and Isabelle Migeotte and Ercan Mihci and Banu Nur and Florence Petit and Juliette Piard and Plasschaert, {Frank S} and Anita Rauch and Pascale Riba{\"i} and Pacheco, {Iratxe Salcedo} and Franco Stanzial and Irene Stolte-Dijkstra and Irene Valenzuela and Vinod Varghese and Vasudevan, {Pradeep C} and Emma Wakeling and Carina Wallgren-Pettersson and Paul Coucke and {De Paepe}, Anne and {De Wolf}, Dani{\"e}l and Sofie Symoens and Bert Callewaert",

year = "2020",

month = jan,

doi = "10.1038/s41436-019-0609-8",

language = "English",

volume = "22",

pages = "124--131",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "1",

}

Meerschaut, I, De Coninck, S, Steyaert, W, Barnicoat, A, Bayat, A, Benedicenti, F, Berland, S, Blair, EM, Breckpot, J, de Burca, A, Destrée, A, García-Miñaúr, S, Green, AJ, Hanna, BC, Keymolen, K, Koopmans, M, Lederer, D, Lees, M, Longman, C, Lynch, SA, Male, AM, McKenzie, F, Migeotte, I, Mihci, E, Nur, B, Petit, F, Piard, J, Plasschaert, FS, Rauch, A, Ribaï, P, Pacheco, IS, Stanzial, F, Stolte-Dijkstra, I, Valenzuela, I, Varghese, V, Vasudevan, PC, Wakeling, E, Wallgren-Pettersson, C, Coucke, P, De Paepe, A, De Wolf, D, Symoens, S & Callewaert, B 2020, 'A clinical scoring system for congenital contractural arachnodactyly', Genetics in Medicine, bind 22, nr. 1, s. 124-131. https://doi.org/10.1038/s41436-019-0609-8

TY - JOUR

T1 - A clinical scoring system for congenital contractural arachnodactyly

AU - Meerschaut, Ilse

AU - De Coninck, Shana

AU - Steyaert, Wouter

AU - Barnicoat, Angela

AU - Bayat, Allan

AU - Benedicenti, Francesco

AU - Berland, Siren

AU - Blair, Edward M

AU - Breckpot, Jeroen

AU - de Burca, Anna

AU - Destrée, Anne

AU - García-Miñaúr, Sixto

AU - Green, Andrew J

AU - Hanna, Bernadette C

AU - Keymolen, Kathelijn

AU - Koopmans, Marije

AU - Lederer, Damien

AU - Lees, Melissa

AU - Longman, Cheryl

AU - Lynch, Sally Ann

AU - Male, Alison M

AU - McKenzie, Fiona

AU - Migeotte, Isabelle

AU - Mihci, Ercan

AU - Nur, Banu

AU - Petit, Florence

AU - Piard, Juliette

AU - Plasschaert, Frank S

AU - Rauch, Anita

AU - Ribaï, Pascale

AU - Pacheco, Iratxe Salcedo

AU - Stanzial, Franco

AU - Stolte-Dijkstra, Irene

AU - Valenzuela, Irene

AU - Varghese, Vinod

AU - Vasudevan, Pradeep C

AU - Wakeling, Emma

AU - Wallgren-Pettersson, Carina

AU - Coucke, Paul

AU - De Paepe, Anne

AU - De Wolf, Daniël

AU - Symoens, Sofie

AU - Callewaert, Bert

PY - 2020/1

Y1 - 2020/1

N2 - PURPOSE: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder manifesting joint contractures, arachnodactyly, crumpled ears, and kyphoscoliosis as main features. Due to its rarity, rather aspecific clinical presentation, and overlap with other conditions including Marfan syndrome, the diagnosis is challenging, but important for prognosis and clinical management. CCA is caused by pathogenic variants in FBN2, encoding fibrillin-2, but locus heterogeneity has been suggested. We designed a clinical scoring system and diagnostic criteria to support the diagnostic process and guide molecular genetic testing.METHODS: In this retrospective study, we assessed 167 probands referred for FBN2 analysis and classified them into a FBN2-positive (n = 44) and FBN2-negative group (n = 123) following molecular analysis. We developed a 20-point weighted clinical scoring system based on the prevalence of ten main clinical characteristics of CCA in both groups.RESULTS: The total score was significantly different between the groups (P < 0.001) and was indicative for classifying patients into unlikely CCA (total score <7) and likely CCA (total score ≥7) groups.CONCLUSIONS: Our clinical score is helpful for clinical guidance for patients suspected to have CCA, and provides a quantitative tool for phenotyping in research settings.

AB - PURPOSE: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder manifesting joint contractures, arachnodactyly, crumpled ears, and kyphoscoliosis as main features. Due to its rarity, rather aspecific clinical presentation, and overlap with other conditions including Marfan syndrome, the diagnosis is challenging, but important for prognosis and clinical management. CCA is caused by pathogenic variants in FBN2, encoding fibrillin-2, but locus heterogeneity has been suggested. We designed a clinical scoring system and diagnostic criteria to support the diagnostic process and guide molecular genetic testing.METHODS: In this retrospective study, we assessed 167 probands referred for FBN2 analysis and classified them into a FBN2-positive (n = 44) and FBN2-negative group (n = 123) following molecular analysis. We developed a 20-point weighted clinical scoring system based on the prevalence of ten main clinical characteristics of CCA in both groups.RESULTS: The total score was significantly different between the groups (P < 0.001) and was indicative for classifying patients into unlikely CCA (total score <7) and likely CCA (total score ≥7) groups.CONCLUSIONS: Our clinical score is helpful for clinical guidance for patients suspected to have CCA, and provides a quantitative tool for phenotyping in research settings.

KW - Arachnodactyly/diagnosis

KW - Child

KW - Contracture/diagnosis

KW - Diagnosis, Differential

KW - Early Diagnosis

KW - Female

KW - Fibrillin-2/genetics

KW - Genetic Testing

KW - Humans

KW - Male

KW - Marfan Syndrome/diagnosis

KW - Phenotype

KW - Retrospective Studies

KW - Sensitivity and Specificity

KW - Sequence Analysis, DNA/methods

U2 - 10.1038/s41436-019-0609-8

DO - 10.1038/s41436-019-0609-8

M3 - Article

C2 - 31316167

SN - 1098-3600

VL - 22

SP - 124

EP - 131

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 1

ER -

A clinical scoring system for congenital contractural arachnodactyly

Abstract

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