Cornelia de Lange syndrome in diverse populations

Leah Dowsett, Antonio R. Porras, Paul Kruszka, Brandon Davis, Tommy Hu, Engela Honey, Eben Badoe, Meow Keong Thong, Eyby Leon, Katta M. Girisha, Anju Shukla, Shalini S. Nayak, Vorasuk Shotelersuk, Andre Megarbane, Shubha Phadke, Nirmala D. Sirisena, Vajira H.W. Dissanayake, Carlos R. Ferreira, Monisha S. Kisling, Pranoot Tanpaiboon & 45 others Annette Uwineza, Leon Mutesa, Cedrik Tekendo-Ngongang, Ambroise Wonkam, Karen Fieggen, Leticia Cassimiro Batista, Danilo Moretti-Ferreira, Roger E. Stevenson, Eloise J. Prijoles, David Everman, Kate Clarkson, Jessica Worthington, Virginia Kimonis, Fuki Hisama, Carol Crowe, Paul Wong, Kisha Johnson, Robin D. Clark, Lynne Bird, Diane Masser-Frye, Marie McDonald, Patrick Willems, Elizabeth Roeder, Sulgana Saitta, Kwame Anyane-Yeoba, Laurie Demmer, Naoki Hamajima, Zornitza Stark, Greta Gillies, Louanne Hudgins, Usha Dave, Stavit Shalev, Victoria Siu, Ann Ades, Holly Dubbs, Sarah Raible, Maninder Kaur, Emanuela Salzano, Laird Jackson, Matthew Deardorff, Antonie Kline, Marshall Summar, Maximilian Muenke, Marius George Linguraru, Ian D. Krantz

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Cornelia de Lange syndrome (CdLS) is a dominant multisystemic malformation syndrome due to mutations in five genes—NIPBL, SMC1A, HDAC8, SMC3, and RAD21. The characteristic facial dysmorphisms include microcephaly, arched eyebrows, synophrys, short nose with depressed bridge and anteverted nares, long philtrum, thin lips, micrognathia, and hypertrichosis. Most affected individuals have intellectual disability, growth deficiency, and upper limb anomalies. This study looked at individuals from diverse populations with both clinical and molecularly confirmed diagnoses of CdLS by facial analysis technology. Clinical data and images from 246 individuals with CdLS were obtained from 15 countries. This cohort included 49% female patients and ages ranged from infancy to 37 years. Individuals were grouped into ancestry categories of African descent, Asian, Latin American, Middle Eastern, and Caucasian. Across these populations, 14 features showed a statistically significant difference. The most common facial features found in all ancestry groups included synophrys, short nose with anteverted nares, and a long philtrum with thin vermillion of the upper lip. Using facial analysis technology we compared 246 individuals with CdLS to 246 gender/age matched controls and found that sensitivity was equal or greater than 95% for all groups. Specificity was equal or greater than 91%. In conclusion, we present consistent clinical findings from global populations with CdLS while demonstrating how facial analysis technology can be a tool to support accurate diagnoses in the clinical setting. This work, along with prior studies in this arena, will assist in earlier detection, recognition, and treatment of CdLS worldwide.

Original languageEnglish
Pages (from-to)150-158
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Volume179
Issue number2
DOIs
Publication statusPublished - 01-02-2019

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De Lange Syndrome
Lip
Population
Technology
Nose
Micrognathism
Hypertrichosis
Eyebrows
Microcephaly
Asian Americans
Upper Extremity
Intellectual Disability
Mutation
Growth

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Dowsett, L., Porras, A. R., Kruszka, P., Davis, B., Hu, T., Honey, E., ... Krantz, I. D. (2019). Cornelia de Lange syndrome in diverse populations. American Journal of Medical Genetics, Part A, 179(2), 150-158. https://doi.org/10.1002/ajmg.a.61033
Dowsett, Leah ; Porras, Antonio R. ; Kruszka, Paul ; Davis, Brandon ; Hu, Tommy ; Honey, Engela ; Badoe, Eben ; Thong, Meow Keong ; Leon, Eyby ; Girisha, Katta M. ; Shukla, Anju ; Nayak, Shalini S. ; Shotelersuk, Vorasuk ; Megarbane, Andre ; Phadke, Shubha ; Sirisena, Nirmala D. ; Dissanayake, Vajira H.W. ; Ferreira, Carlos R. ; Kisling, Monisha S. ; Tanpaiboon, Pranoot ; Uwineza, Annette ; Mutesa, Leon ; Tekendo-Ngongang, Cedrik ; Wonkam, Ambroise ; Fieggen, Karen ; Batista, Leticia Cassimiro ; Moretti-Ferreira, Danilo ; Stevenson, Roger E. ; Prijoles, Eloise J. ; Everman, David ; Clarkson, Kate ; Worthington, Jessica ; Kimonis, Virginia ; Hisama, Fuki ; Crowe, Carol ; Wong, Paul ; Johnson, Kisha ; Clark, Robin D. ; Bird, Lynne ; Masser-Frye, Diane ; McDonald, Marie ; Willems, Patrick ; Roeder, Elizabeth ; Saitta, Sulgana ; Anyane-Yeoba, Kwame ; Demmer, Laurie ; Hamajima, Naoki ; Stark, Zornitza ; Gillies, Greta ; Hudgins, Louanne ; Dave, Usha ; Shalev, Stavit ; Siu, Victoria ; Ades, Ann ; Dubbs, Holly ; Raible, Sarah ; Kaur, Maninder ; Salzano, Emanuela ; Jackson, Laird ; Deardorff, Matthew ; Kline, Antonie ; Summar, Marshall ; Muenke, Maximilian ; Linguraru, Marius George ; Krantz, Ian D. / Cornelia de Lange syndrome in diverse populations. In: American Journal of Medical Genetics, Part A. 2019 ; Vol. 179, No. 2. pp. 150-158.
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abstract = "Cornelia de Lange syndrome (CdLS) is a dominant multisystemic malformation syndrome due to mutations in five genes—NIPBL, SMC1A, HDAC8, SMC3, and RAD21. The characteristic facial dysmorphisms include microcephaly, arched eyebrows, synophrys, short nose with depressed bridge and anteverted nares, long philtrum, thin lips, micrognathia, and hypertrichosis. Most affected individuals have intellectual disability, growth deficiency, and upper limb anomalies. This study looked at individuals from diverse populations with both clinical and molecularly confirmed diagnoses of CdLS by facial analysis technology. Clinical data and images from 246 individuals with CdLS were obtained from 15 countries. This cohort included 49{\%} female patients and ages ranged from infancy to 37 years. Individuals were grouped into ancestry categories of African descent, Asian, Latin American, Middle Eastern, and Caucasian. Across these populations, 14 features showed a statistically significant difference. The most common facial features found in all ancestry groups included synophrys, short nose with anteverted nares, and a long philtrum with thin vermillion of the upper lip. Using facial analysis technology we compared 246 individuals with CdLS to 246 gender/age matched controls and found that sensitivity was equal or greater than 95{\%} for all groups. Specificity was equal or greater than 91{\%}. In conclusion, we present consistent clinical findings from global populations with CdLS while demonstrating how facial analysis technology can be a tool to support accurate diagnoses in the clinical setting. This work, along with prior studies in this arena, will assist in earlier detection, recognition, and treatment of CdLS worldwide.",
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Dowsett, L, Porras, AR, Kruszka, P, Davis, B, Hu, T, Honey, E, Badoe, E, Thong, MK, Leon, E, Girisha, KM, Shukla, A, Nayak, SS, Shotelersuk, V, Megarbane, A, Phadke, S, Sirisena, ND, Dissanayake, VHW, Ferreira, CR, Kisling, MS, Tanpaiboon, P, Uwineza, A, Mutesa, L, Tekendo-Ngongang, C, Wonkam, A, Fieggen, K, Batista, LC, Moretti-Ferreira, D, Stevenson, RE, Prijoles, EJ, Everman, D, Clarkson, K, Worthington, J, Kimonis, V, Hisama, F, Crowe, C, Wong, P, Johnson, K, Clark, RD, Bird, L, Masser-Frye, D, McDonald, M, Willems, P, Roeder, E, Saitta, S, Anyane-Yeoba, K, Demmer, L, Hamajima, N, Stark, Z, Gillies, G, Hudgins, L, Dave, U, Shalev, S, Siu, V, Ades, A, Dubbs, H, Raible, S, Kaur, M, Salzano, E, Jackson, L, Deardorff, M, Kline, A, Summar, M, Muenke, M, Linguraru, MG & Krantz, ID 2019, 'Cornelia de Lange syndrome in diverse populations' American Journal of Medical Genetics, Part A, vol. 179, no. 2, pp. 150-158. https://doi.org/10.1002/ajmg.a.61033

Cornelia de Lange syndrome in diverse populations. / Dowsett, Leah; Porras, Antonio R.; Kruszka, Paul; Davis, Brandon; Hu, Tommy; Honey, Engela; Badoe, Eben; Thong, Meow Keong; Leon, Eyby; Girisha, Katta M.; Shukla, Anju; Nayak, Shalini S.; Shotelersuk, Vorasuk; Megarbane, Andre; Phadke, Shubha; Sirisena, Nirmala D.; Dissanayake, Vajira H.W.; Ferreira, Carlos R.; Kisling, Monisha S.; Tanpaiboon, Pranoot; Uwineza, Annette; Mutesa, Leon; Tekendo-Ngongang, Cedrik; Wonkam, Ambroise; Fieggen, Karen; Batista, Leticia Cassimiro; Moretti-Ferreira, Danilo; Stevenson, Roger E.; Prijoles, Eloise J.; Everman, David; Clarkson, Kate; Worthington, Jessica; Kimonis, Virginia; Hisama, Fuki; Crowe, Carol; Wong, Paul; Johnson, Kisha; Clark, Robin D.; Bird, Lynne; Masser-Frye, Diane; McDonald, Marie; Willems, Patrick; Roeder, Elizabeth; Saitta, Sulgana; Anyane-Yeoba, Kwame; Demmer, Laurie; Hamajima, Naoki; Stark, Zornitza; Gillies, Greta; Hudgins, Louanne; Dave, Usha; Shalev, Stavit; Siu, Victoria; Ades, Ann; Dubbs, Holly; Raible, Sarah; Kaur, Maninder; Salzano, Emanuela; Jackson, Laird; Deardorff, Matthew; Kline, Antonie; Summar, Marshall; Muenke, Maximilian; Linguraru, Marius George; Krantz, Ian D.

In: American Journal of Medical Genetics, Part A, Vol. 179, No. 2, 01.02.2019, p. 150-158.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cornelia de Lange syndrome in diverse populations

AU - Dowsett, Leah

AU - Porras, Antonio R.

AU - Kruszka, Paul

AU - Davis, Brandon

AU - Hu, Tommy

AU - Honey, Engela

AU - Badoe, Eben

AU - Thong, Meow Keong

AU - Leon, Eyby

AU - Girisha, Katta M.

AU - Shukla, Anju

AU - Nayak, Shalini S.

AU - Shotelersuk, Vorasuk

AU - Megarbane, Andre

AU - Phadke, Shubha

AU - Sirisena, Nirmala D.

AU - Dissanayake, Vajira H.W.

AU - Ferreira, Carlos R.

AU - Kisling, Monisha S.

AU - Tanpaiboon, Pranoot

AU - Uwineza, Annette

AU - Mutesa, Leon

AU - Tekendo-Ngongang, Cedrik

AU - Wonkam, Ambroise

AU - Fieggen, Karen

AU - Batista, Leticia Cassimiro

AU - Moretti-Ferreira, Danilo

AU - Stevenson, Roger E.

AU - Prijoles, Eloise J.

AU - Everman, David

AU - Clarkson, Kate

AU - Worthington, Jessica

AU - Kimonis, Virginia

AU - Hisama, Fuki

AU - Crowe, Carol

AU - Wong, Paul

AU - Johnson, Kisha

AU - Clark, Robin D.

AU - Bird, Lynne

AU - Masser-Frye, Diane

AU - McDonald, Marie

AU - Willems, Patrick

AU - Roeder, Elizabeth

AU - Saitta, Sulgana

AU - Anyane-Yeoba, Kwame

AU - Demmer, Laurie

AU - Hamajima, Naoki

AU - Stark, Zornitza

AU - Gillies, Greta

AU - Hudgins, Louanne

AU - Dave, Usha

AU - Shalev, Stavit

AU - Siu, Victoria

AU - Ades, Ann

AU - Dubbs, Holly

AU - Raible, Sarah

AU - Kaur, Maninder

AU - Salzano, Emanuela

AU - Jackson, Laird

AU - Deardorff, Matthew

AU - Kline, Antonie

AU - Summar, Marshall

AU - Muenke, Maximilian

AU - Linguraru, Marius George

AU - Krantz, Ian D.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Cornelia de Lange syndrome (CdLS) is a dominant multisystemic malformation syndrome due to mutations in five genes—NIPBL, SMC1A, HDAC8, SMC3, and RAD21. The characteristic facial dysmorphisms include microcephaly, arched eyebrows, synophrys, short nose with depressed bridge and anteverted nares, long philtrum, thin lips, micrognathia, and hypertrichosis. Most affected individuals have intellectual disability, growth deficiency, and upper limb anomalies. This study looked at individuals from diverse populations with both clinical and molecularly confirmed diagnoses of CdLS by facial analysis technology. Clinical data and images from 246 individuals with CdLS were obtained from 15 countries. This cohort included 49% female patients and ages ranged from infancy to 37 years. Individuals were grouped into ancestry categories of African descent, Asian, Latin American, Middle Eastern, and Caucasian. Across these populations, 14 features showed a statistically significant difference. The most common facial features found in all ancestry groups included synophrys, short nose with anteverted nares, and a long philtrum with thin vermillion of the upper lip. Using facial analysis technology we compared 246 individuals with CdLS to 246 gender/age matched controls and found that sensitivity was equal or greater than 95% for all groups. Specificity was equal or greater than 91%. In conclusion, we present consistent clinical findings from global populations with CdLS while demonstrating how facial analysis technology can be a tool to support accurate diagnoses in the clinical setting. This work, along with prior studies in this arena, will assist in earlier detection, recognition, and treatment of CdLS worldwide.

AB - Cornelia de Lange syndrome (CdLS) is a dominant multisystemic malformation syndrome due to mutations in five genes—NIPBL, SMC1A, HDAC8, SMC3, and RAD21. The characteristic facial dysmorphisms include microcephaly, arched eyebrows, synophrys, short nose with depressed bridge and anteverted nares, long philtrum, thin lips, micrognathia, and hypertrichosis. Most affected individuals have intellectual disability, growth deficiency, and upper limb anomalies. This study looked at individuals from diverse populations with both clinical and molecularly confirmed diagnoses of CdLS by facial analysis technology. Clinical data and images from 246 individuals with CdLS were obtained from 15 countries. This cohort included 49% female patients and ages ranged from infancy to 37 years. Individuals were grouped into ancestry categories of African descent, Asian, Latin American, Middle Eastern, and Caucasian. Across these populations, 14 features showed a statistically significant difference. The most common facial features found in all ancestry groups included synophrys, short nose with anteverted nares, and a long philtrum with thin vermillion of the upper lip. Using facial analysis technology we compared 246 individuals with CdLS to 246 gender/age matched controls and found that sensitivity was equal or greater than 95% for all groups. Specificity was equal or greater than 91%. In conclusion, we present consistent clinical findings from global populations with CdLS while demonstrating how facial analysis technology can be a tool to support accurate diagnoses in the clinical setting. This work, along with prior studies in this arena, will assist in earlier detection, recognition, and treatment of CdLS worldwide.

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Dowsett L, Porras AR, Kruszka P, Davis B, Hu T, Honey E et al. Cornelia de Lange syndrome in diverse populations. American Journal of Medical Genetics, Part A. 2019 Feb 1;179(2):150-158. https://doi.org/10.1002/ajmg.a.61033