KBG syndrome

KBG syndrome is an inherited developmental condition that affects multiple body systems, especially the skeleton, teeth, and nervous system. It results from changes in the ANKRD11 gene, which encodes a protein that helps regulate the activity of many other genes during early growth. Signs usually become apparent in infancy or early childhood when caregivers notice developmental delays, short stature, or distinctive facial and dental features. The condition is very rare, affecting fewer than one person in a million worldwide, and it can occur in both males and females. Although life-threatening complications are uncommon, most individuals benefit from lifelong medical and educational support.

The most recognizable feature of KBG syndrome is macrodontia, meaning the permanent upper front teeth are unusually large and often appear earlier than expected. Distinctive facial characteristics include a triangular face, long philtrum, wide-set eyes, anteverted nostrils, and sometimes ptosis of the eyelids. Skeletal involvement is broad: children typically have delayed bone age, short stature, short palms, fifth-finger clinodactyly, and in some cases extra cervical ribs or other costovertebral anomalies. Neurologically, all reported individuals have some degree of intellectual or developmental disability, and a minority experience seizures. Additional findings can include protruding or posteriorly rotated ears, thick or low hairlines, cryptorchidism in males, and subtle differences in skull shape such as brachycephaly. Not all individuals experience all features, and severity varies considerably from one person to another. Early concerns often relate to developmental milestones or feeding and speech difficulties, while orthopedic or dental issues may become more apparent with growth.

KBG syndrome is caused by pathogenic variants in the ANKRD11 gene. The ANKRD11 protein influences how other genes turn on and off during development, so disrupted function can affect many tissues at once. The condition follows an autosomal dominant inheritance pattern, meaning one altered copy of the gene is sufficient to cause symptoms. An affected parent has a 50 percent chance of passing the variant to each child. Even within the same family, the specific features and their severity can vary considerably, a concept known as variable expressivity. Genetic counseling is recommended for families to understand personal recurrence risks and discuss testing options for relatives.

Currently, management focuses on supportive care and symptom management. Early intervention services, speech and occupational therapy, and individualized educational plans help address intellectual and developmental needs. Orthodontic or dental care can manage macrodontia and associated bite issues, while orthopedic assessment is important for spinal or rib anomalies and short stature. Seizures, when present, are treated with standard antiepileptic medications under neurologist guidance. Because many body systems can be involved, long-term care is typically coordinated by a multidisciplinary team that may include pediatricians, geneticists, neurologists, dentists, orthopedic surgeons, and endocrinologists. Regular surveillance is an essential part of long-term care, helping to detect potential complications such as progressive spinal curvature, hearing issues, or growth concerns before they become serious. Families should discuss individualized monitoring schedules and available therapies with their healthcare providers, and genetic counseling can aid in family planning decisions.

Most individuals with KBG syndrome have a normal life span, but they often live with chronic challenges related to learning, behavior, and skeletal health. Severity and symptoms vary widely between individuals, even within the same family. With timely therapies, many children make meaningful developmental progress, attend school, and participate in community activities, although independent living as adults may require supports. Orthopedic problems and dental issues can continue to need attention during adolescence and adulthood. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with KBG syndrome and with patient support organizations to share experiences and learn about new resources.

Clinical trials are underway exploring new treatment approaches and deepening understanding of ANKRD11 function. Areas of interest include clarifying how different variants alter protein activity and how early interventions influence developmental outcomes. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.