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Although the prevalence of the disorder is unknown, it is thought to be less than 1/1,000,000. To date, 122 individuals with molecularly diagnosed blepharophimosis-intellectual disability syndrome, SBBYS type (SBBYS), have been reported.

Clinical diagnosis is typically based on the striking facial gestalt associated with microcephaly. Skeletal anomalies include long thumbs and great toes, patellar hypoplasia/agenesis, polydactyly (both pre and postaxial), camptodactyly, clinodactyly, brachydactyly, syndactyly, club feet , flexion contractures of the knees and/or hips, and anomalies of the spine, and/or ribs. Individuals generally have developmental delay/intellectual disability, which can be mild. Language disorder, autism spectrum features, anxiety, aggressiveness, attention problems, agenesis or hypoplasia of the corpus callosum, optic nerve hypoplasia and other brain abnormalities have also been reported. Congenital heart malformations (50% of cases), ocular anomalies and bilateral mixed hearing loss are also often present. Renal anomalies (e.g. hydronephrosis or multiple renal cysts), anal and genital anomalies including cryptorchidism, hypospadias, clitoromegaly and/or hypoplasia of the labia minora or majora, are reported in more than 40% of cases. In a minority of cases, thyroid agenesis/hypoplasia, hypothyroidism, intestinal malrotation, dental anomalies, feeding and respiratory difficulties, gastroesophageal reflux, poor growth, short stature, cleft palate, and Pierre Robin sequence are observed. SBBYS is allelic with genitopatellar syndrome and an intermediate phenotype has been described; thus, the disorder may present as part of a spectrum.

The syndrome is caused by heterozygous variants in KAT6B (10q22) encoding a highly conserved acetyltransferase that is part of the MYST family, and regulates the expression of multiple genes.

Diagnosis is based on clinical examination, brain imaging and molecular studies (specific gene testing if the specific clinical suspicion has been raised, otherwise broader genomic tests).

Differential diagnosis include other genetic syndromes that associates intellectual disability with one or more of the key features of this disorder.

Polyhydramnios, increased nuchal translucency and/or cystic hygroma, renal anomalies can be observed during pregnancy but are non-specific. Genetic diagnosis can be proposed to families in which the pathogenic variant has already been identified in an affected relative.

Transmission is autosomal dominant. Most of the cases described are de novo, so the empirical risk of recurrence is low, 1-2%. Three families have been described in which the pathogenic variant has been inherited from a parent with a mild phenotype. The recurrence risk in these cases is 50%. To date, no cases of germinal mosaicism have been reported but this cannot be excluded.

Management requires a lifelong multidisciplinary approach with specific regular follow-up based on the patient's clinical manifestations (pediatric, neuropsychiatric, cardiological, ophthalmological, audiometric, orpthopedic, and genetic examinations). Occupational, physical, speech (in particular non-verbal methods of communication), feeding and educational therapies must be tailored to the patient's needs. Bowel malrotation is a potentially dangerous medical complication. Particular attention should be paid to monitoring feeding and growth, as feeding problems tend to occur early.

Whilst there is limited data regarding life expectancy, adult patients are reported and there are no known reasons to suspect reduced life expectancy. Autonomy depends on the degree of involvement and the severity of the psychomotor developmental delay.