Cornelia de Lange syndrome in diverse populations

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, lon...

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Published in:	American journal of medical genetics. Part A Vol. 179; no. 2; pp. 150 - 158
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	Hoboken, USA John Wiley & Sons, Inc 01-02-2019 Wiley Subscription Services, Inc
Subjects:	Abnormalities, Multiple - epidemiology Abnormalities, Multiple - genetics Abnormalities, Multiple - physiopathology Adolescent Adult CdLS Cell Cycle Proteins - genetics Child Child, Preschool Chondroitin Sulfate Proteoglycans - genetics Chromosomal Proteins, Non-Histone - genetics Continental Population Groups - genetics Cornelia de Lange syndrome Data processing De Lange syndrome De Lange Syndrome - epidemiology De Lange Syndrome - genetics De Lange Syndrome - physiopathology diverse populations Face - physiopathology facial analysis technology Female Humans Hypertrichosis Image Processing, Computer-Assisted Infant Infant, Newborn Intellectual Disability - epidemiology Intellectual Disability - genetics Intellectual Disability - physiopathology Male Microcephaly Mutation NIPBL Nose Phenotype Statistical analysis underrepresented minorities Young Adult Cornelia de Lange syndrome NIPBL underrepresented minorities diverse populations facial analysis technology CdLS
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Summary:	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.
Bibliography:	Funding information CdLS Center Endowed Funds, Children's Hospital of Philadelphia; Chulalongkorn Academic Advancement Into Its 2nd Century Project; Division of Intramural Research, National Human Genome Research, NIH; Government of Abu Dhabi ; National Institute of Child Health and Human Development, Grant/Award Number: PO1/HD052860; National Institute of General Medical Sciences, Grant/Award Number: T32/GM008638; PKS Italia; PKSKids USA; Thailand Research Fund ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1552-4825 1552-4833
DOI:	10.1002/ajmg.a.61033