Clinical characteristics: KAT6B disorders include genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) which are part of a broad phenotypic spectrum with variable expressivity; individuals presenting with a phenotype intermediate between GPS and SBBYSS have been reported. Both phenotypes are characterized by some degree of global developmental delay / intellectual disability; hypotonia; genital abnormalities; and skeletal abnormalities including patellar hypoplasia/agenesis, flexion contractures of the knees and/or hips, and anomalies of the digits, spine, and/or ribs. Congenital heart defects, small bowel malrotation, feeding difficulties, slow growth, cleft palate, hearing loss, and dental anomalies have been observed in individuals with either phenotype.
Diagnosis/testing: The diagnosis of a KAT6B disorder is established by the identification of a heterozygous pathogenic variant in KAT6B on molecular genetic testing.
Management: Treatment of manifestations: Medical problems associated with gastrointestinal, genitourinary, cardiac, palatal or dental anomalies; abnormal vision or lacrimal duct abnormality; hearing loss; or hypothyroidism associated with KAT6B disorders are treated or managed in the standard manner by the appropriate specialist. Referral to an early intervention program to access occupational, physical, speech, and feeding therapy beginning in infancy. Orthopedic intervention as needed for contractures and clubfoot; physical therapy to increase joint mobility.
Surveillance: Evaluations of developmental progress and educational needs, assessment for feeding issues, and monitoring for hearing loss, amblyopia, hypothyroidism, and contractures and/or scoliosis should occur annually. Evaluation and monitoring of cardiac malformation and/or renal function (if hydronephrosis or renal cysts are present) as needed.
Genetic counseling: KAT6B disorders are inherited in an autosomal dominant manner. To date, most individuals with a KAT6B disorder have had a de novo pathogenic variant. Prenatal and preimplantation genetic testing are possible for families in which the pathogenic variant has been identified.
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