Noonan syndrome in diverse populations

Paul Kruszka, Antonio R. Porras, Yonit A. Addissie, Angélica Moresco, Sofia Medrano, Gary T.K. Mok, Gordon K.C. Leung, Cedrik Tekendo-Ngongang, Annette Uwineza, Meow Keong Thong, Premala Muthukumarasamy, Engela Honey, Ekanem N. Ekure, Ogochukwu J. Sokunbi, Nnenna Kalu, Kelly L. Jones, Julie D. Kaplan, Omar A. Abdul-Rahman, Lisa M. Vincent, Amber Love & 42 others Khadija Belhassan, Karim Ouldim, Ihssane El Bouchikhi, Anju Shukla, Katta M. Girisha, Siddaramappa J. Patil, Nirmala D. Sirisena, Vajira H.W. Dissanayake, C. Sampath Paththinige, Rupesh Mishra, Eva Klein-Zighelboim, Bertha E. Gallardo Jugo, Miguel Chávez Pastor, Hugo H. Abarca-Barriga, Steven A. Skinner, Eloise J. Prijoles, Eben Badoe, Ashleigh D. Gill, Vorasuk Shotelersuk, Patroula Smpokou, Monisha S. Kisling, Carlos R. Ferreira, Leon Mutesa, Andre Megarbane, Antonie D. Kline, Amy Kimball, Emmy Okello, Peter Lwabi, Twalib Aliku, Emmanuel Tenywa, Nonglak Boonchooduang, Pranoot Tanpaiboon, Antonio Richieri-Costa, Ambroise Wonkam, Brian H.Y. Chung, Roger E. Stevenson, Marshall Summar, Kausik Mandal, Shubha R. Phadke, María G. Obregon, Marius G. Linguraru, Maximilian Muenke

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.

Original languageEnglish
Pages (from-to)2323-2334
Number of pages12
JournalAmerican Journal of Medical Genetics, Part A
Volume173
Issue number9
DOIs
Publication statusPublished - 01-09-2017

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Noonan Syndrome
Population
Asian Americans
Technology
Population Groups
Pulmonary Valve Stenosis
ras Genes
Ear
Phenotype

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Kruszka, P., Porras, A. R., Addissie, Y. A., Moresco, A., Medrano, S., Mok, G. T. K., ... Muenke, M. (2017). Noonan syndrome in diverse populations. American Journal of Medical Genetics, Part A, 173(9), 2323-2334. https://doi.org/10.1002/ajmg.a.38362
Kruszka, Paul ; Porras, Antonio R. ; Addissie, Yonit A. ; Moresco, Angélica ; Medrano, Sofia ; Mok, Gary T.K. ; Leung, Gordon K.C. ; Tekendo-Ngongang, Cedrik ; Uwineza, Annette ; Thong, Meow Keong ; Muthukumarasamy, Premala ; Honey, Engela ; Ekure, Ekanem N. ; Sokunbi, Ogochukwu J. ; Kalu, Nnenna ; Jones, Kelly L. ; Kaplan, Julie D. ; Abdul-Rahman, Omar A. ; Vincent, Lisa M. ; Love, Amber ; Belhassan, Khadija ; Ouldim, Karim ; El Bouchikhi, Ihssane ; Shukla, Anju ; Girisha, Katta M. ; Patil, Siddaramappa J. ; Sirisena, Nirmala D. ; Dissanayake, Vajira H.W. ; Paththinige, C. Sampath ; Mishra, Rupesh ; Klein-Zighelboim, Eva ; Gallardo Jugo, Bertha E. ; Chávez Pastor, Miguel ; Abarca-Barriga, Hugo H. ; Skinner, Steven A. ; Prijoles, Eloise J. ; Badoe, Eben ; Gill, Ashleigh D. ; Shotelersuk, Vorasuk ; Smpokou, Patroula ; Kisling, Monisha S. ; Ferreira, Carlos R. ; Mutesa, Leon ; Megarbane, Andre ; Kline, Antonie D. ; Kimball, Amy ; Okello, Emmy ; Lwabi, Peter ; Aliku, Twalib ; Tenywa, Emmanuel ; Boonchooduang, Nonglak ; Tanpaiboon, Pranoot ; Richieri-Costa, Antonio ; Wonkam, Ambroise ; Chung, Brian H.Y. ; Stevenson, Roger E. ; Summar, Marshall ; Mandal, Kausik ; Phadke, Shubha R. ; Obregon, María G. ; Linguraru, Marius G. ; Muenke, Maximilian. / Noonan syndrome in diverse populations. In: American Journal of Medical Genetics, Part A. 2017 ; Vol. 173, No. 9. pp. 2323-2334.
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abstract = "Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46{\%}. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80{\%} or greater of participants, short stature in more than 70{\%}, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94{\%} for all groups, and specificity was equal to or greater than 90{\%}. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.",
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Kruszka, P, Porras, AR, Addissie, YA, Moresco, A, Medrano, S, Mok, GTK, Leung, GKC, Tekendo-Ngongang, C, Uwineza, A, Thong, MK, Muthukumarasamy, P, Honey, E, Ekure, EN, Sokunbi, OJ, Kalu, N, Jones, KL, Kaplan, JD, Abdul-Rahman, OA, Vincent, LM, Love, A, Belhassan, K, Ouldim, K, El Bouchikhi, I, Shukla, A, Girisha, KM, Patil, SJ, Sirisena, ND, Dissanayake, VHW, Paththinige, CS, Mishra, R, Klein-Zighelboim, E, Gallardo Jugo, BE, Chávez Pastor, M, Abarca-Barriga, HH, Skinner, SA, Prijoles, EJ, Badoe, E, Gill, AD, Shotelersuk, V, Smpokou, P, Kisling, MS, Ferreira, CR, Mutesa, L, Megarbane, A, Kline, AD, Kimball, A, Okello, E, Lwabi, P, Aliku, T, Tenywa, E, Boonchooduang, N, Tanpaiboon, P, Richieri-Costa, A, Wonkam, A, Chung, BHY, Stevenson, RE, Summar, M, Mandal, K, Phadke, SR, Obregon, MG, Linguraru, MG & Muenke, M 2017, 'Noonan syndrome in diverse populations', American Journal of Medical Genetics, Part A, vol. 173, no. 9, pp. 2323-2334. https://doi.org/10.1002/ajmg.a.38362

Noonan syndrome in diverse populations. / Kruszka, Paul; Porras, Antonio R.; Addissie, Yonit A.; Moresco, Angélica; Medrano, Sofia; Mok, Gary T.K.; Leung, Gordon K.C.; Tekendo-Ngongang, Cedrik; Uwineza, Annette; Thong, Meow Keong; Muthukumarasamy, Premala; Honey, Engela; Ekure, Ekanem N.; Sokunbi, Ogochukwu J.; Kalu, Nnenna; Jones, Kelly L.; Kaplan, Julie D.; Abdul-Rahman, Omar A.; Vincent, Lisa M.; Love, Amber; Belhassan, Khadija; Ouldim, Karim; El Bouchikhi, Ihssane; Shukla, Anju; Girisha, Katta M.; Patil, Siddaramappa J.; Sirisena, Nirmala D.; Dissanayake, Vajira H.W.; Paththinige, C. Sampath; Mishra, Rupesh; Klein-Zighelboim, Eva; Gallardo Jugo, Bertha E.; Chávez Pastor, Miguel; Abarca-Barriga, Hugo H.; Skinner, Steven A.; Prijoles, Eloise J.; Badoe, Eben; Gill, Ashleigh D.; Shotelersuk, Vorasuk; Smpokou, Patroula; Kisling, Monisha S.; Ferreira, Carlos R.; Mutesa, Leon; Megarbane, Andre; Kline, Antonie D.; Kimball, Amy; Okello, Emmy; Lwabi, Peter; Aliku, Twalib; Tenywa, Emmanuel; Boonchooduang, Nonglak; Tanpaiboon, Pranoot; Richieri-Costa, Antonio; Wonkam, Ambroise; Chung, Brian H.Y.; Stevenson, Roger E.; Summar, Marshall; Mandal, Kausik; Phadke, Shubha R.; Obregon, María G.; Linguraru, Marius G.; Muenke, Maximilian.

In: American Journal of Medical Genetics, Part A, Vol. 173, No. 9, 01.09.2017, p. 2323-2334.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Noonan syndrome in diverse populations

AU - Kruszka, Paul

AU - Porras, Antonio R.

AU - Addissie, Yonit A.

AU - Moresco, Angélica

AU - Medrano, Sofia

AU - Mok, Gary T.K.

AU - Leung, Gordon K.C.

AU - Tekendo-Ngongang, Cedrik

AU - Uwineza, Annette

AU - Thong, Meow Keong

AU - Muthukumarasamy, Premala

AU - Honey, Engela

AU - Ekure, Ekanem N.

AU - Sokunbi, Ogochukwu J.

AU - Kalu, Nnenna

AU - Jones, Kelly L.

AU - Kaplan, Julie D.

AU - Abdul-Rahman, Omar A.

AU - Vincent, Lisa M.

AU - Love, Amber

AU - Belhassan, Khadija

AU - Ouldim, Karim

AU - El Bouchikhi, Ihssane

AU - Shukla, Anju

AU - Girisha, Katta M.

AU - Patil, Siddaramappa J.

AU - Sirisena, Nirmala D.

AU - Dissanayake, Vajira H.W.

AU - Paththinige, C. Sampath

AU - Mishra, Rupesh

AU - Klein-Zighelboim, Eva

AU - Gallardo Jugo, Bertha E.

AU - Chávez Pastor, Miguel

AU - Abarca-Barriga, Hugo H.

AU - Skinner, Steven A.

AU - Prijoles, Eloise J.

AU - Badoe, Eben

AU - Gill, Ashleigh D.

AU - Shotelersuk, Vorasuk

AU - Smpokou, Patroula

AU - Kisling, Monisha S.

AU - Ferreira, Carlos R.

AU - Mutesa, Leon

AU - Megarbane, Andre

AU - Kline, Antonie D.

AU - Kimball, Amy

AU - Okello, Emmy

AU - Lwabi, Peter

AU - Aliku, Twalib

AU - Tenywa, Emmanuel

AU - Boonchooduang, Nonglak

AU - Tanpaiboon, Pranoot

AU - Richieri-Costa, Antonio

AU - Wonkam, Ambroise

AU - Chung, Brian H.Y.

AU - Stevenson, Roger E.

AU - Summar, Marshall

AU - Mandal, Kausik

AU - Phadke, Shubha R.

AU - Obregon, María G.

AU - Linguraru, Marius G.

AU - Muenke, Maximilian

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.

AB - Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.

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Kruszka P, Porras AR, Addissie YA, Moresco A, Medrano S, Mok GTK et al. Noonan syndrome in diverse populations. American Journal of Medical Genetics, Part A. 2017 Sep 1;173(9):2323-2334. https://doi.org/10.1002/ajmg.a.38362