2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Novel de novo Intronic <em>KAT6B </em>Variant in 9-year-old Female Adds to the Wide Phenotypic Spectrum of <em>KAT6B</em> Disorders

Novel de novo Intronic KAT6B Variant in 9-year-old Female Adds to the Wide Phenotypic Spectrum of KAT6B Disorders

Pdf Summary

A 9-year-old female patient presented with a range of physical and developmental symptoms, including malar flattening, expressionless facies, up-slanting and small palpebral fissures, retrognathia, tubular nose, red keratosis, hypertelorism, esotropia, low-set and small ears, and skeletal differences such as proximally placed long thumbs and short 5th metacarpals, and shortened 5th metatarsals, long 3rd and 4th toes, shortened great toes, and significant pes planus. Whole exome sequencing revealed a novel de novo intronic variant in the KAT6B gene, which is associated with KAT6B disorders, including Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS). This variant was likely pathogenic and predicted to have a deleterious effect. It is worth noting that loss-of-function is a known mechanism of disease in the KAT6B gene. The patient did not exhibit gross motor delay but presented with classic SBBYSS facial features and psychiatric issues, including anxiety, ADHD, obsessive tendencies, defiant behaviors, and features suggestive of autism spectrum disorder. The patient also had a variant of uncertain significance (VUS) in the TRRAP gene inherited from the mother, which could contribute to her phenotype. TRRAP-related disorders have a variable phenotype and may include dysmorphic facies, developmental delay, congenital anomalies, visual and hearing abnormalities, microcephaly, and seizures. This case adds to the literature on intronic variants causing KAT6B disorders and expands the wide phenotypic spectrum associated with these disorders.

Asset Subtitle

Co-Author - Lingying Liu, CGC; Presenting Author - Paul R. Hillman, MD/PhD;

Meta Tag

Phenotypic delineation of disorders

Phenotype

Musculoskeletal system

Genotype-Phenotype Correlations

Exome sequencing

Delineation of Diseases

Cognitive Disorders

Clinical History

Co-Author Lingying Liu, CGC

Presenting Author Paul R. Hillman, MD/PhD

Keywords

9-year-old female patient

physical symptoms

developmental symptoms

KAT6B gene

KAT6B disorders

SBBYSS facial features

psychiatric issues

autism spectrum disorder

TRRAP gene

TRRAP-related disorders