Citations 2
Expanding the phenotype of ASXL3‐related syndrome: A comprehensive description of 45 unpublished individuals with inherited and de novo pathogenic variants in ASXL3
Schirwani, Schaida , Albaba, Shadi , Carere, Deanna Alexis , Sacoto, María J. Guillen , Zamora, Francisca Milan, Si, Yue , Rabin, Rachel , Renaud, Deborah L. , Hauser, Natalie , Blanchet, Patricia, Foulds, Nichola, Dixit, Abhijit , Fisher, Richard, Armstrong, Ruth, Isidor, Bertrand , Demirdas, Serwet , Dykzeul, Natalie, Cohen, Julie S. , Grand, Katheryn , Swols, Dayna Morel , Albassam, Hessa F., Naik, Swati , Ragge, Nicola , Tedesco, Maria Giovanna , Harrison, Rachel , Bouman, Arjan , Palen, Emily, Challman, Thomas D. , Willemsen, Marjolein H. , Vogt, Julie , Cunniff, Christopher , Bergstrom, Katherine , Bruel, Ange‐Line , Kini, Usha , Alkuraya, Fowzan S. , Slegesky, Valerie, Meeks, Naomi, Girotto, Paula Natale , Johnson, Diana , Study, DDD, Newbury‐Ecob, Ruth , Lynch, Sally Ann , Graham, John M. , Balasubramanian, Meena , Hauser, Natalie , Schrier Vergano, Samantha , Bouman, Arjan , Cunniff, Christopher , Bergstrom, Katherine , Bruel, Ange-Line , Alkuraya, Fowzan S , Prontera, Paolo , Li, Dong , Graham, John M , Zamora, Francisca Millan, Pappas, John , Reid, Evan , Cogné, Benjamin , Vergano, Samantha A. Schrier , Slavotinek, Anne , Naik, Swati, Dean, John , Costa, Cinzia , Walia, Jagdeep Singh , Study, DDD, Ockeloen, Charlotte W. , Li, Dong , Pierson, Tyler Mark
American Journal of Medical Genetics Part A | August 26, 2021 | Volume: 185 | Issue: 11 | Pages: 3446-3458
AbstractThe study aimed at widening the clinical and genetic spectrum of ASXL3‐related syndrome, a neurodevelopmental disorder, caused by truncating variants in the ASXL3 gene. In this international collaborative study, we have undertaken a detailed clinical and molecular analysis of 45 previously unpublished individuals with ASXL3‐related syndrome, as well as a review of all previously published individuals. We have reviewed the rather limited functional characterization of pathogenic variants in ASXL3 and discuss current understanding of the consequences of the different ASXL3 variants. In this comprehensive analysis of ASXL3‐related syndrome, we define its natural history and clinical evolution occurring with age. We report familial ASXL3 pathogenic variants, characterize the phenotype in mildly affected individuals and discuss nonpenetrance. We also discuss the role of missense variants in ASXL3. We delineate a variable but consistent phenotype. The most characteristic features are neurodevelopmental delay with consistently limited speech, significant neuro‐behavioral issues, hypotonia, and feeding difficulties. Distinctive features include downslanting palpebral fissures, hypertelorism, tubular nose with a prominent nasal bridge, and low‐hanging columella. The presented data will inform clinical management of individuals with ASXL3‐related syndrome and improve interpretation of new ASXL3 sequence variants.
Clinical delineation of the PACS1‐related syndrome—Report on 19 patients
Schuurs-Hoeijmakers, Janneke , Landsverk, Megan , Foulds, Nicola , Kukolich, Mary K. , Gavrilova, Ralitza H. , Greville‐Heygate, Stephanie , Hanson‐Kahn, Andrea , Bernstein, Jonathan A. , Glass, Jennifer, Burrow, Thomas Andrew, Husami, Ammar , Collins, Kathleen , Wusik, Katie, Aa, Nathalie Van der, Kooy, R. Frank , Brown, Kate Tatton, Gadzicki, Dorothea, Kini, Usha , McGehee, Frank T., Selby, Katherine, Tarailo‐Graovac, Maja , Allen, Margot Van, Stavropoulos, Dimitri J. , Marshall, Christian R. , Merico, Daniele , Gregor, Anne , Zweier, Christiane , Chu, Yoyo W. Y., Vries, Bert B.A. de , Brunner, Han G. , study, DDD, Chitayat, David A. , Collins, Kathleen , Álvarez, Sara , Fernández‐Jaén, Alberto , Allen, Margot I. Van, Karnebeek, Clara van , Hopkin, Robert J. , Chung, Hon-Yin B , Devriendt, Koenraad , Hurles, Matthew E. , study, DDD, Kooy, Frank , de Vries, Bert B A
American Journal of Medical Genetics Part A | February 4, 2016 | Volume: 170 | Issue: 3 | Pages: 670-675
We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual “wavy” profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work‐up and management and hope that the present study will facilitate clinical recognition of further cases. © 2016 Wiley Periodicals, Inc.