Sleep disturbance is a common feature of Kabuki syndrome

Tyler Rapp; Allison J. Kalinousky; Jennifer Johnson; Hans Tómas Björnsson; Jacqueline Harris

doi:10.1002/ajmg.a.62921

Sleep disturbance is a common feature of Kabuki syndrome

Tyler Rapp
, Allison J. Kalinousky
, Jennifer Johnson
, Hans Tómas Björnsson
, Jacqueline Harris

University of Iceland, Landspitali

Research output: Contribution to journal › Article › peer-review

Abstract

Kabuki syndrome (KS) is a rare epigenetic disorder caused by heterozygous loss of function variants in either KMT2D (90%) or KDM6A (10%), both involved in regulation of histone methylation. While sleep disturbance in other Mendelian disorders of the epigenetic machinery has been reported, no study has been conducted on sleep in KS. This study assessed sleep in 59 participants with KS using a validated sleep questionnaire. Participants ranged in age from 4 to 43 years old with 86% of participants having a pathogenic variant in KMT2D. In addition, data on adaptive function, behavior, anxiety, and quality of life were collected using their respective questionnaires. Some form of sleep issue was present in 71% of participants, with night-waking, daytime sleepiness, and sleep onset delay being the most prevalent. Sleep dysfunction was positively correlated with maladaptive behaviors, anxiety levels, and decreasing quality of life. Sleep issues were not correlated with adaptive function. This study establishes sleep disturbance as a common feature of KS. Quantitative sleep measures may be a useful outcome measure for clinical trials in KS. Further, clinicians caring for those with KS should consider sleep dysfunction as an important feature that impacts overall health and well being in these patients.

Original language	English
Pages (from-to)	3041-3048
Number of pages	8
Journal	American Journal of Medical Genetics, Part A
Volume	188
Issue number	10
DOIs	https://doi.org/10.1002/ajmg.a.62921
Publication status	Published - 5 Aug 2022

Bibliographical note

Funding Information: Icelandic Research Fund, Grant/Award Number: 217988 195835 206806; Icelandic Technology Development Fund, Grant/Award Number: 2010588; Kabuki Syndrome Foundation; Kennedy Krieger IDDRC NIH, Grant/Award Number: P50HD103538; NIH/NICHD, Grant/Award Number: K23HD101646; Rubinstein‐Taybi Syndrome Children‧s Foundation; Sekel‐Breidenstein Family Fund Funding information Funding Information: This research received no direct external funding. Hans Bjornsson is supported by grants from the Louma G. Foundation, the Icelandic Research Fund (#217988, #195835, #206806) and the Icelandic Technology Development Fund (#2010588). Jacqueline Harris is supported by grants from the NIH/NICHD K23HD101646, the Kabuki Syndrome Foundation, the Rubinstein‐Taybi Syndrome Children's Foundation, the Sekel‐Breidenstein Family Fund, and the Kennedy Krieger IDDRC NIH P50HD103538. Funding Information: The authors express their gratitude to all the families that participated in this study. We also thank the Kabuki Syndrome Foundation and All Things Kabuki who helped promote this study. Publisher Copyright: © 2022 Wiley Periodicals LLC.

Other keywords

Abnormalities, Multiple
Adolescent
Adult
Child
Child, Preschool
Face/abnormalities
Hematologic Diseases/complications
Histone Demethylases/genetics
Humans
KDM6A
KMT2D
MLL2
Mutation
Quality of Life
Sleep
Vestibular Diseases/complications
Young Adult
epigenetics
neurodevelopmental

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10.1002/ajmg.a.62921

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@article{24c5a99379f7495685f4443509259df9,

title = "Sleep disturbance is a common feature of Kabuki syndrome",

abstract = "Kabuki syndrome (KS) is a rare epigenetic disorder caused by heterozygous loss of function variants in either KMT2D (90\%) or KDM6A (10\%), both involved in regulation of histone methylation. While sleep disturbance in other Mendelian disorders of the epigenetic machinery has been reported, no study has been conducted on sleep in KS. This study assessed sleep in 59 participants with KS using a validated sleep questionnaire. Participants ranged in age from 4 to 43 years old with 86\% of participants having a pathogenic variant in KMT2D. In addition, data on adaptive function, behavior, anxiety, and quality of life were collected using their respective questionnaires. Some form of sleep issue was present in 71\% of participants, with night-waking, daytime sleepiness, and sleep onset delay being the most prevalent. Sleep dysfunction was positively correlated with maladaptive behaviors, anxiety levels, and decreasing quality of life. Sleep issues were not correlated with adaptive function. This study establishes sleep disturbance as a common feature of KS. Quantitative sleep measures may be a useful outcome measure for clinical trials in KS. Further, clinicians caring for those with KS should consider sleep dysfunction as an important feature that impacts overall health and well being in these patients.",

keywords = "Abnormalities, Multiple, Adolescent, Adult, Child, Child, Preschool, Face/abnormalities, Hematologic Diseases/complications, Histone Demethylases/genetics, Humans, KDM6A, KMT2D, MLL2, Mutation, Quality of Life, Sleep, Vestibular Diseases/complications, Young Adult, epigenetics, neurodevelopmental",

author = "Tyler Rapp and Kalinousky, \{Allison J.\} and Jennifer Johnson and Bj{\"o}rnsson, \{Hans T{\'o}mas\} and Jacqueline Harris",

note = "Funding Information: Icelandic Research Fund, Grant/Award Number: 217988 195835 206806; Icelandic Technology Development Fund, Grant/Award Number: 2010588; Kabuki Syndrome Foundation; Kennedy Krieger IDDRC NIH, Grant/Award Number: P50HD103538; NIH/NICHD, Grant/Award Number: K23HD101646; Rubinstein‐Taybi Syndrome Children‧s Foundation; Sekel‐Breidenstein Family Fund Funding information Funding Information: This research received no direct external funding. Hans Bjornsson is supported by grants from the Louma G. Foundation, the Icelandic Research Fund (\#217988, \#195835, \#206806) and the Icelandic Technology Development Fund (\#2010588). Jacqueline Harris is supported by grants from the NIH/NICHD K23HD101646, the Kabuki Syndrome Foundation, the Rubinstein‐Taybi Syndrome Children's Foundation, the Sekel‐Breidenstein Family Fund, and the Kennedy Krieger IDDRC NIH P50HD103538. Funding Information: The authors express their gratitude to all the families that participated in this study. We also thank the Kabuki Syndrome Foundation and All Things Kabuki who helped promote this study. Publisher Copyright: {\textcopyright} 2022 Wiley Periodicals LLC.",

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doi = "10.1002/ajmg.a.62921",

language = "English",

volume = "188",

pages = "3041--3048",

journal = "American Journal of Medical Genetics, Part A",

issn = "1552-4825",

publisher = "John Wiley and Sons Inc.",

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AU - Rapp, Tyler

AU - Kalinousky, Allison J.

AU - Johnson, Jennifer

AU - Björnsson, Hans Tómas

AU - Harris, Jacqueline

N1 - Funding Information: Icelandic Research Fund, Grant/Award Number: 217988 195835 206806; Icelandic Technology Development Fund, Grant/Award Number: 2010588; Kabuki Syndrome Foundation; Kennedy Krieger IDDRC NIH, Grant/Award Number: P50HD103538; NIH/NICHD, Grant/Award Number: K23HD101646; Rubinstein‐Taybi Syndrome Children‧s Foundation; Sekel‐Breidenstein Family Fund Funding information Funding Information: This research received no direct external funding. Hans Bjornsson is supported by grants from the Louma G. Foundation, the Icelandic Research Fund (#217988, #195835, #206806) and the Icelandic Technology Development Fund (#2010588). Jacqueline Harris is supported by grants from the NIH/NICHD K23HD101646, the Kabuki Syndrome Foundation, the Rubinstein‐Taybi Syndrome Children's Foundation, the Sekel‐Breidenstein Family Fund, and the Kennedy Krieger IDDRC NIH P50HD103538. Funding Information: The authors express their gratitude to all the families that participated in this study. We also thank the Kabuki Syndrome Foundation and All Things Kabuki who helped promote this study. Publisher Copyright: © 2022 Wiley Periodicals LLC.

PY - 2022/8/5

Y1 - 2022/8/5

N2 - Kabuki syndrome (KS) is a rare epigenetic disorder caused by heterozygous loss of function variants in either KMT2D (90%) or KDM6A (10%), both involved in regulation of histone methylation. While sleep disturbance in other Mendelian disorders of the epigenetic machinery has been reported, no study has been conducted on sleep in KS. This study assessed sleep in 59 participants with KS using a validated sleep questionnaire. Participants ranged in age from 4 to 43 years old with 86% of participants having a pathogenic variant in KMT2D. In addition, data on adaptive function, behavior, anxiety, and quality of life were collected using their respective questionnaires. Some form of sleep issue was present in 71% of participants, with night-waking, daytime sleepiness, and sleep onset delay being the most prevalent. Sleep dysfunction was positively correlated with maladaptive behaviors, anxiety levels, and decreasing quality of life. Sleep issues were not correlated with adaptive function. This study establishes sleep disturbance as a common feature of KS. Quantitative sleep measures may be a useful outcome measure for clinical trials in KS. Further, clinicians caring for those with KS should consider sleep dysfunction as an important feature that impacts overall health and well being in these patients.

AB - Kabuki syndrome (KS) is a rare epigenetic disorder caused by heterozygous loss of function variants in either KMT2D (90%) or KDM6A (10%), both involved in regulation of histone methylation. While sleep disturbance in other Mendelian disorders of the epigenetic machinery has been reported, no study has been conducted on sleep in KS. This study assessed sleep in 59 participants with KS using a validated sleep questionnaire. Participants ranged in age from 4 to 43 years old with 86% of participants having a pathogenic variant in KMT2D. In addition, data on adaptive function, behavior, anxiety, and quality of life were collected using their respective questionnaires. Some form of sleep issue was present in 71% of participants, with night-waking, daytime sleepiness, and sleep onset delay being the most prevalent. Sleep dysfunction was positively correlated with maladaptive behaviors, anxiety levels, and decreasing quality of life. Sleep issues were not correlated with adaptive function. This study establishes sleep disturbance as a common feature of KS. Quantitative sleep measures may be a useful outcome measure for clinical trials in KS. Further, clinicians caring for those with KS should consider sleep dysfunction as an important feature that impacts overall health and well being in these patients.

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KW - Adult

KW - Child

KW - Child, Preschool

KW - Face/abnormalities

KW - Hematologic Diseases/complications

KW - Histone Demethylases/genetics

KW - Humans

KW - KDM6A

KW - KMT2D

KW - MLL2

KW - Mutation

KW - Quality of Life

KW - Sleep

KW - Vestibular Diseases/complications

KW - Young Adult

KW - epigenetics

KW - neurodevelopmental

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DO - 10.1002/ajmg.a.62921

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SN - 1552-4825

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SP - 3041

EP - 3048

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

IS - 10

ER -

Sleep disturbance is a common feature of Kabuki syndrome

Abstract

Bibliographical note

Other keywords

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