Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) are part of a broad phenotypic spectrum, and the variable expressivity of KAT6B disorders is increasingly being recognized. Individuals presenting with a phenotype intermediate between GPS and SBBYSS have been reported in the past years. Both phenotypes are characterized by some degree of global developmental delay / intellectual disability; hypotonia and feeding difficulties. Congenital heart defects, hearing loss, hypothyroidism, dental anomalies and growth delay have been observed in individuals with either phenotype.
GPS: Nearly all individuals with GPS have agenesis or hypoplasia of the corpus callosum
Patellae are either absent or hypoplastic in the majority of affected individuals. Club feet and flexion contractures of the knees and/or hips are also present in nearly all individuals with GPS. Genitourinary anomalies are frequently present in individuals affected by GPS, including cryptorchidism, scrotal hypoplasia, micropenis, hypospadias, clitoromegaly and/or hypoplasia of the labia (minora or majora). Many individuals have renal anomalies, especially hydronephrosis and multicystic kidneys.
SBBYSS: Blepharophimosis is a major feature of SBBYSS and it can impact visual function. Lacrimal duct anomalies, mainly dacryostenosis, are found in many individuals with SBBYSS. Most individuals have long thumbs and great toes. Facial appearance is distinctive with a mask-like facies and ptosis. Genital anomalies are frequently present.
We suggest using the following approach to determine the clinical subtype that best corresponds to an individual with a KAT6B variant:
1. KAT6B disorder, GPS subtype (at least two major features suggesting GPS)
2. KAT6B disorder, SBBYSS subtype (at least two major features suggesting SBBYSS)
3. KAT6B disorder, intermediate subtype (at least two major features of both GPS and SBBYSS, excluding patellar anomalies)
4. KAT6B disorder, subtype not otherwise specified (cannot be classified in subtypes 1, 2 or 3)
Major features suggestive of GPS | Major features suggestive of SBBYSS |
• Genital anomalies | • Long thumbs/great toes |
• Patellar hypoplasia/agenesis | • Patellar hypoplasia/agenesis |
• Contractures at the hips, knees and/or clubfoot | • Immotile mask-like facies |
• Agenesis of the corpus callosum | • Blepharophimosis and/or ptosis |
• Renal anomalies (e.g., hydronephrosis or multiple renal cysts) | • Lacrimal duct anomalies |