Further delineation of the clinical spectrum of KAT6B disorders and allelic series of pathogenic variants.
Genet Med
; 22(8): 1338-1347, 2020 08.
Article
in En
| MEDLINE
| ID: mdl-32424177
ABSTRACT
PURPOSE:
Genitopatellar syndrome and Say-Barber-Biesecker-Young-Simpson syndrome are caused by variants in the KAT6B gene and are part of a broad clinical spectrum called KAT6B disorders, whose variable expressivity is increasingly being recognized.METHODS:
We herein present the phenotypes of 32 previously unreported individuals with a molecularly confirmed diagnosis of a KAT6B disorder, report 24 new pathogenic KAT6B variants, and review phenotypic information available on all published individuals with this condition. We also suggest a classification of clinical subtypes within the KAT6B disorder spectrum.RESULTS:
We demonstrate that cerebral anomalies, optic nerve hypoplasia, neurobehavioral difficulties, and distal limb anomalies other than long thumbs and great toes, such as polydactyly, are more frequently observed than initially reported. Intestinal malrotation and its serious consequences can be present in affected individuals. Additionally, we identified four children with Pierre Robin sequence, four individuals who had increased nuchal translucency/cystic hygroma prenatally, and two fetuses with severe renal anomalies leading to renal failure. We also report an individual in which a pathogenic variant was inherited from a mildly affected parent.CONCLUSION:
Our work provides a comprehensive review and expansion of the genotypic and phenotypic spectrum of KAT6B disorders that will assist clinicians in the assessment, counseling, and management of affected individuals.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blepharophimosis
/
Intellectual Disability
Limits:
Humans
Language:
En
Journal:
Genet Med
Journal subject:
GENETICA MEDICA
Year:
2020
Document type:
Article
Affiliation country:
Publication country:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA