KBG syndrome

What KBG syndrome is

KBG syndrome was first described by Herrmann and colleagues in 1975 in three families whose surnames began with K, B and G — the initials still used as the syndrome's name. For decades it was diagnosed only when the most striking features were present, but next-generation sequencing has revealed a much broader picture: mild as well as severe presentations, and parents who only learn they have the syndrome after their child is diagnosed.

It is now considered one of the more common ANKRD11-related conditions. Many older children and adults are being newly diagnosed when whole-exome or panel testing is done for unexplained learning difficulties or short stature.

The genetic cause (ANKRD11)

ANKRD11 makes a protein involved in regulating gene expression — particularly in growth-plate cells, neurons and tooth-forming cells. Loss of one working copy (haploinsufficiency) produces the recognisable mix of growth, skeletal, dental and neurodevelopmental features.

About half of all cases are de novo, and the other half are inherited from a parent who often has a milder version of the syndrome and may not yet have been diagnosed. Recurrence risk for siblings is therefore higher than for many other neurodevelopmental syndromes (50% for the child of an affected parent), which makes family genetic counselling important.

Both intragenic variants and microdeletions involving 16q24.3 cause KBG syndrome; the chromosomal version often includes features beyond the typical KBG picture.

How it presents

• Distinctive facial appearance: triangular face, broad full eyebrows that may meet in the middle (synophrys), a long philtrum, thin upper lip and prominent ears
• Macrodontia of the upper central incisors — large, prominent permanent upper front teeth, often noticed when adult teeth come through
• Short stature and delayed bone age; growth slows in early childhood
• Skeletal features: short fifth fingers with clinodactyly, vertebral anomalies, sometimes mild scoliosis, broad great toes
• Mild to moderate intellectual disability and global developmental delay; speech is often the most delayed area
• Behaviour: ADHD is very common, autism spectrum features in a sizeable minority, sometimes anxiety
• Seizures in roughly 30% of children — usually well-controlled with standard antiseizure medicines
• Hearing loss (conductive or mixed), recurrent ear infections, wide or persistent anterior fontanelle in infancy, a hoarse or husky voice

Investigations and diagnosis

Genetic diagnosis is made by detecting a heterozygous pathogenic ANKRD11 variant — through chromosomal microarray (for deletions), gene panel testing, or whole-exome/whole-genome sequencing. A clinical scoring system based on facial appearance, dental features, skeletal findings and developmental delay can be useful, but genetic testing remains essential because the milder presentations are easily missed.

Standard assessments at diagnosis include audiology (hearing), ophthalmology, dental review (especially of the developing dentition), spine X-ray when scoliosis is suspected, an echocardiogram (because of occasional congenital heart defects), and a developmental and behavioural evaluation. Because parents may share the syndrome, parental testing is offered.

Current management

There is no targeted therapy, and management is symptomatic and supportive. With early multidisciplinary input most children make steady progress, attend mainstream or specialised schools depending on their level of need, and reach a meaningful degree of independence in adulthood.

• Early developmental, speech and occupational therapy from infancy
• ADHD and anxiety are often the most disabling daily issues — standard medical and behavioural treatments work well and should not be delayed
• Audiology follow-up and prompt management of conductive hearing loss (grommets, hearing aids) to protect language development
• Dental review and orthodontic planning as the adult dentition appears
• Growth hormone therapy has been reported in case series and small studies for the short-stature phenotype, with positive effects on growth velocity in some children — but it is not standard of care and requires endocrinology assessment
• Spine surveillance for scoliosis through adolescence; cardiology follow-up when a heart defect is present
• Seizures are managed with standard antiseizure medicines; no medicine is preferentially avoided

The research landscape

There is no disease-modifying clinical trial open in KBG syndrome as of 2026, and no targeted drug or gene therapy in clinical development at present. Active research is mostly in three areas: (1) better understanding of the genotype–phenotype relationship, particularly for the wide range of intellectual disability seen across the syndrome; (2) systematic descriptions of growth-hormone response and orthopaedic outcomes; and (3) preclinical work on the molecular role of ANKRD11 in brain development. Family organisations such as the KBG Foundation maintain registries and family-led natural-history projects that could support future trials.

How an educational review can help

If your child has — or might have — KBG syndrome, an educational review can pull together the multidisciplinary picture (growth, dentition, skeletal, hearing, behaviour, seizures), explain which assessments are worth prioritising, and clarify which features merit ongoing surveillance into adolescence and adulthood. It is educational and supports your treating clinicians.