Rubinstein-Taybi syndrome in diverse populations

Cedrik Tekendo-Ngongang¹, Babajide Owosela¹, Nicole Fleischer², Yonit A Addissie¹, Bryan Malonga¹, Ebenezer Badoe³, Neerja Gupta⁴, Angélica Moresco⁵, Victoria Huckstadt⁵, Engy A Ashaat⁶, Dalia Farouk Hussen⁷, Ho-Ming Luk⁸, Ivan F M Lo⁸, Brian Hon-Yin Chung⁹, Jasmine L F Fung⁹, Danilo Moretti-Ferreira¹⁰, Letícia Cassimiro Batista¹⁰, Stephanie Lotz-Esquivel¹¹, Manuel Saborio-Rocafort¹², Ramses Badilla-Porras¹², Monica Penon Portmann^{12

13}, Kelly L Jones¹⁴, Omar A Abdul-Rahman¹⁵, Annette Uwineza¹⁶, Eloise J Prijoles¹⁷, Ifeanyi Kanayo Ifeorah¹⁸, Arianne Llamos Paneque¹⁹, Nirmala D Sirisena²⁰, Leah Dowsett²¹, Sansan Lee²¹, Gerarda Cappuccio^{22

23}, Carolyn Sian Kitchin²⁴, Alicia Diaz-Kuan²⁵, Meow-Keong Thong²⁶, María Gabriela Obregon⁵, Leon Mutesa¹⁶, Vajira H W Dissanayake²⁰, Mona O El Ruby⁶, Nicola Brunetti-Pierri^{22

23}, Ekanem Nsikak Ekure²⁷, Roger E Stevenson¹⁷, Maximilian Muenke¹, Paul Kruszka¹

Affiliations

¹ Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland, USA.
² FDNA Inc., Boston, Massachusetts, USA.
³ Department of Child Health, School of Medicine and Dentistry, College of Health Sciences, Accra, Ghana.
⁴ Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
⁵ Servicio de Genética, Hospital de Pediatría Garrahan, Buenos Aires, Argentina.
⁶ Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
⁷ Cytogenetic Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
⁸ Department of Health, Clinical Genetic Service, Hong Kong Special Administrative Region, Hong Kong, China.
⁹ Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.
¹⁰ Department of Genetics, Institute of Biosciences, Sao Paulo State University-UNESP, Botucatu, São Paulo, Brazil.
¹¹ Rare and Orphan Disease Multidisciplinary Clinic, Hospital San Juan de Dios (CCSS), San José, Costa Rica.
¹² Medical Genetics and Metabolism Department, National Children's Hospital "Dr. Carlos Sáenz Herrera" (CCSS), San José, Costa Rica.
¹³ Division of Medical Genetics, Department of Pediatrics & Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA.
¹⁴ Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA.
¹⁵ Munroe-Meyer institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska, USA.
¹⁶ Centre for Human Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
¹⁷ Greenwood Genetic Center, Greenwood, South Carolina, USA.
¹⁸ Nigerian Air Force Hospital, Nigerian Air Force, Abuja, Nigeria.
¹⁹ Medical Genetics Service, Specialty Hospital of the Armed Forces No. 1, International University of Ecuador, Sciences of Life Faculty, School of Dentistry, Quito, Ecuador.
²⁰ Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
²¹ Kapi'olani Medical Center and University of Hawai'i, Honolulu, Hawaii, USA.
²² Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy.
²³ Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
²⁴ Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
²⁵ Instituto de Medicina Genética, Santiago de Surco, Lima, Peru.
²⁶ Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
²⁷ Department of Paediatrics, College of Medicine, University of Lagos, Lagos, Nigeria.

PMID: 32985117
DOI: 10.1002/ajmg.a.61888

Rubinstein-Taybi syndrome in diverse populations

Cedrik Tekendo-Ngongang et al. Am J Med Genet A. 2020 Dec.

. 2020 Dec;182(12):2939-2950.

doi: 10.1002/ajmg.a.61888. Epub 2020 Sep 27.

Authors

Affiliations

¹ Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland, USA.
² FDNA Inc., Boston, Massachusetts, USA.
³ Department of Child Health, School of Medicine and Dentistry, College of Health Sciences, Accra, Ghana.
⁴ Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
⁵ Servicio de Genética, Hospital de Pediatría Garrahan, Buenos Aires, Argentina.
⁶ Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
⁷ Cytogenetic Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
⁸ Department of Health, Clinical Genetic Service, Hong Kong Special Administrative Region, Hong Kong, China.
⁹ Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.
¹⁰ Department of Genetics, Institute of Biosciences, Sao Paulo State University-UNESP, Botucatu, São Paulo, Brazil.
¹¹ Rare and Orphan Disease Multidisciplinary Clinic, Hospital San Juan de Dios (CCSS), San José, Costa Rica.
¹² Medical Genetics and Metabolism Department, National Children's Hospital "Dr. Carlos Sáenz Herrera" (CCSS), San José, Costa Rica.
¹³ Division of Medical Genetics, Department of Pediatrics & Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA.
¹⁴ Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA.
¹⁵ Munroe-Meyer institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska, USA.
¹⁶ Centre for Human Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
¹⁷ Greenwood Genetic Center, Greenwood, South Carolina, USA.
¹⁸ Nigerian Air Force Hospital, Nigerian Air Force, Abuja, Nigeria.
¹⁹ Medical Genetics Service, Specialty Hospital of the Armed Forces No. 1, International University of Ecuador, Sciences of Life Faculty, School of Dentistry, Quito, Ecuador.
²⁰ Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
²¹ Kapi'olani Medical Center and University of Hawai'i, Honolulu, Hawaii, USA.
²² Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy.
²³ Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
²⁴ Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
²⁵ Instituto de Medicina Genética, Santiago de Surco, Lima, Peru.
²⁶ Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
²⁷ Department of Paediatrics, College of Medicine, University of Lagos, Lagos, Nigeria.

PMID: 32985117
DOI: 10.1002/ajmg.a.61888

Abstract

Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant disorder, caused by loss-of-function variants in CREBBP or EP300. Affected individuals present with distinctive craniofacial features, broad thumbs and/or halluces, and intellectual disability. RSTS phenotype has been well characterized in individuals of European descent but not in other populations. In this study, individuals from diverse populations with RSTS were assessed by clinical examination and facial analysis technology. Clinical data of 38 individuals from 14 different countries were analyzed. The median age was 7 years (age range: 7 months to 47 years), and 63% were females. The most common phenotypic features in all population groups included broad thumbs and/or halluces in 97%, convex nasal ridge in 94%, and arched eyebrows in 92%. Face images of 87 individuals with RSTS (age range: 2 months to 47 years) were collected for evaluation using facial analysis technology. We compared images from 82 individuals with RSTS against 82 age- and sex-matched controls and obtained an area under the receiver operating characteristic curve (AUC) of 0.99 (p < .001), demonstrating excellent discrimination efficacy. The discrimination was, however, poor in the African group (AUC: 0.79; p = .145). Individuals with EP300 variants were more effectively discriminated (AUC: 0.95) compared with those with CREBBP variants (AUC: 0.93). This study shows that clinical examination combined with facial analysis technology may enable earlier and improved diagnosis of RSTS in diverse populations.

Keywords: Africa; Asia; Latin America; Middle East; Rubinstein-Taybi syndrome; facial analysis technology.

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References

REFERENCES

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1. Bartsch, O., Labonte, J., Albrecht, B., Wieczorek, D., Lechno, S., Zechner, U., & Haaf, T. (2010). Two patients with EP300 mutations and facial dysmorphism different from the classic Rubinstein-Taybi syndrome. American Journal of Medical Genetics, Part A, 152(1), 181-184. https://doi.org/10.1002/ajmg.a.33153
1. Bartsch, O., Wagner, A., Hinkel, G. K., Krebs, P., Stumm, M., Schmalenberger, B., … Majewski, F. (1999). FISH studies in 45 patients with Rubinstein-Taybi syndrome: Deletions associated with polysplenia, hypoplastic left heart and death in infancy. European Journal of Human Genetics, 7(7), 748-756. https://doi.org/10.1038/sj.ejhg.5200378

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Rubinstein-Taybi syndrome in diverse populations

Affiliations

Rubinstein-Taybi syndrome in diverse populations

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous