Insights into the perinatal phenotype of Kabuki syndrome in infants identified by genome-wide sequencing

Kristen Wigby^{1

2}, Monia Hammer², Mari Tokita², Priyanka Patel¹, Marilyn C Jones¹, Austin Larson³, Frances Velez Bartolomei^{4

5}, Natalie Dykzeul⁵, Anne Slavotinek^{6

7}, Tiffany Yip⁶, Sara Bandres-Ciga⁸, Brittany N Simpson⁷, Kristen Suhrie^{9

10}, Suma Shankar¹¹, Regan Veith¹², Jennifer Bragg¹³, Cynthia Powell¹⁴, Stephen F Kingsmore², David Dimmock¹⁵, Jill Maron^{16

17

18}, Jonathan Davis^{17

19}, Miguel Del Campo¹

Affiliations

¹ Department of Pediatrics, Division of Genetics, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, California, USA.
² Rady Children's Institute for Genomic Medicine, San Diego, California, USA.
³ Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
⁴ Torre Medica del San Jorge Hospital, San Juan, Puerto Rico, USA.
⁵ Department of Pediatrics, Division of Genetics, Stanford University, Palo Alto, California, USA.
⁶ Department of Pediatrics, Division of Genetics, University of California San Francisco, San Francisco, California, USA.
⁷ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
⁸ Center for Alzheimer's Disease and Related Dementias (CARD), National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, Maryland, USA.
⁹ Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁰ Department of Genetics, Division of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹¹ Department of Pediatrics, Division of Genetics, University of California, Davis, Sacramento, California, USA.
¹² Children's Minnesota, Minneapolis, Minnesota, USA.
¹³ Department of Pediatrics, Division of Newborn Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁴ Department of Pediatrics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
¹⁵ Creyon Bio Inc, San Diego, California, USA.
¹⁶ Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, USA.
¹⁷ Department of Pediatrics, The Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts, USA.
¹⁸ Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
¹⁹ The Tufts Clinical and Translation Science Institute, Tufts University School of Medicine, Boston, Massachusetts, USA.

PMID: 36651673
DOI: 10.1002/ajmg.a.63097

Insights into the perinatal phenotype of Kabuki syndrome in infants identified by genome-wide sequencing

Kristen Wigby et al. Am J Med Genet A. 2023 Apr.

. 2023 Apr;191(4):930-940.

doi: 10.1002/ajmg.a.63097. Epub 2023 Jan 18.

Authors

Affiliations

¹ Department of Pediatrics, Division of Genetics, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, California, USA.
² Rady Children's Institute for Genomic Medicine, San Diego, California, USA.
³ Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
⁴ Torre Medica del San Jorge Hospital, San Juan, Puerto Rico, USA.
⁵ Department of Pediatrics, Division of Genetics, Stanford University, Palo Alto, California, USA.
⁶ Department of Pediatrics, Division of Genetics, University of California San Francisco, San Francisco, California, USA.
⁷ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
⁸ Center for Alzheimer's Disease and Related Dementias (CARD), National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, Maryland, USA.
⁹ Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁰ Department of Genetics, Division of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹¹ Department of Pediatrics, Division of Genetics, University of California, Davis, Sacramento, California, USA.
¹² Children's Minnesota, Minneapolis, Minnesota, USA.
¹³ Department of Pediatrics, Division of Newborn Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁴ Department of Pediatrics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
¹⁵ Creyon Bio Inc, San Diego, California, USA.
¹⁶ Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, USA.
¹⁷ Department of Pediatrics, The Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts, USA.
¹⁸ Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
¹⁹ The Tufts Clinical and Translation Science Institute, Tufts University School of Medicine, Boston, Massachusetts, USA.

PMID: 36651673
DOI: 10.1002/ajmg.a.63097

Abstract

Increasing use of unbiased genomic sequencing in critically ill infants can expand understanding of rare diseases such as Kabuki syndrome (KS). Infants diagnosed with KS through genome-wide sequencing performed during the initial hospitalization underwent retrospective review of medical records. Human phenotype ontology terms used in genomic analysis were aggregated and analyzed. Clinicians were surveyed regarding changes in management and other care changes. Fifteen infants met inclusion criteria. KS was not suspected prior to genomic sequencing. Variants were classified as Pathogenic (n = 10) or Likely Pathogenic (n = 5) by American College of Medical Genetics and Genomics Guidelines. Fourteen variants were de novo (KMT2D, n = 12, KDM6A, n = 2). One infant inherited a likely pathogenic variant in KMT2D from an affected father. Frequent findings involved cardiovascular (14/15) and renal (7/15) systems, with palatal defects also identified (6/15). Three infants had non-immune hydrops. No minor anomalies were universally documented; ear anomalies, micrognathia, redundant nuchal skin, and hypoplastic nails were common. Changes in management were reported in 14 infants. Early use of unbiased genome-wide sequencing enabled a molecular diagnosis prior to clinical recognition including infants with atypical or rarely reported features of KS while also expanding the phenotypic spectrum of this rare disorder.

Keywords: Kabuki syndrome; infant; phenotype; unbiased genome-wide sequencing.

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References

REFERENCES

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Insights into the perinatal phenotype of Kabuki syndrome in infants identified by genome-wide sequencing

Affiliations

Insights into the perinatal phenotype of Kabuki syndrome in infants identified by genome-wide sequencing

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous