Documentation and prevalence of prenatal and neonatal outcomes in a cohort of individuals with KBG syndrome

Mutations in the Ankyrin Repeat Domain 11 ( ANKRD11 ) gene are associated with KBG syndrome, a developmental disability that affects multiple organ systems and presents with a variety of skeletal, cardiac, gastrointestinal, and neuropsychiatric manifestations. The function of ANKRD11 in human growth and development is not well understood, but its importance is established by the fact that constitutive or conditional gene knockout or mutation are lethal in mice embryos and/or pups. In addition, it plays a vital role in chromatin regulation, transcription, and development. Individuals with KBG syndrome are often misdiagnosed or undiagnosed until later in life, due to a combination of varying phenotypes, lack of targeted prenatal screening, and lack of documentation of prenatal and neonatal symptoms. The present study aims to report perinatal outcomes in individuals with KBG syndrome and their families and compare them to the prevalence in the overall population. We obtained data from 42 individuals through videoconferences, notes, and emails. Our results show that 45.2% of our cohort was born by C-section, 33.3% had a congenital heart defect, 23.8% were born before 37-weeks ‘ gestation, 23.8% were admitted to the NICU, 14.3% were small for gestational age, and 14.3% of the families in our cohort had a history of miscarriage. The prevalence of birth by C-section, premature birth, NICU admission, and small for gestational age was higher in our cohort compared to the overall population, including non-Hispanic and Hispanic populations. Other reports included feeding difficulties (21.4%), neonatal jaundice (14.3%), decreased fetal movement (7.14%), and pleural effusions in utero (4.67%). These findings suggest that there may be an association between ANKRD11 variants or microdeletions and perinatal complications, and further research is needed to better assess the mechanisms behind this relationship. Comprehensive perinatal studies about KBG syndrome and updated documentation of its phenotypes can facilitate earlier detection, diagnosis, and treatment.