Wiedemann-Steiner Syndrome (WSS) is a rare genetic disorder that affects development and multiple body systems. This condition is present from birth, although many of the associated features may become more apparent as a child grows. WSS is characterized by a specific combination of physical traits, developmental delays, and intellectual differences, presenting a broad spectrum of effects across affected individuals. Because the syndrome is rare, a definitive diagnosis often requires advanced genetic testing. Understanding the underlying genetic cause and the common characteristics of WSS is the first step toward providing appropriate, targeted support.
Defining Wiedemann-Steiner Syndrome and its Genetic Cause
Wiedemann-Steiner Syndrome results from a pathogenic variant, or mutation, in the KMT2A gene, located on chromosome 11. This gene, previously known as MLL, is a major regulator of gene expression throughout the body.
The KMT2A gene provides instructions for making an enzyme called a histone methyltransferase. This enzyme acts as an epigenetic regulator, meaning it controls how DNA is read by the cell without changing the core DNA sequence. It modifies histones—proteins that act as spools for DNA—by adding a methyl group.
By modifying these histones, the KMT2A enzyme controls which other genes are “turned on” or “turned off” during early growth and development. A change in KMT2A disrupts this regulatory system, leading to the developmental and physical issues seen in WSS. In the vast majority of cases, the mutation is de novo, meaning it is a spontaneous change not inherited from either parent.
Distinct Physical and Growth Characteristics
Short stature is a common finding, with many individuals falling at the lower end of or below the average height range for their age. In some cases, this slowed growth may be related to a measurable growth hormone deficiency.
A frequently reported feature is hypertrichosis, or excess body hair, which often presents on the back or over the elbows, sometimes called hypertrichosis cubiti. While not every person with WSS has this feature, it is considered a classic characteristic. The craniofacial structure also presents distinct traits, including thick, often bushy eyebrows that may have a characteristic lateral flare toward the temples.
Other common facial characteristics include long, dense eyelashes, widely spaced eyes (telecanthus), and palpebral fissures that may appear vertically narrow or down-slanting. The nose may have a wide bridge and a broad or bulbous tip, sometimes paired with a thin upper lip. These features are subtle and highly variable.
Beyond facial structure, many individuals experience low muscle tone, known as hypotonia, which can contribute to delays in motor skill development. Skeletal findings may include hand anomalies, such as tapered fingertips or shortened digits. Less common but reported issues involve the spine, such as fusion anomalies of the cervical vertebrae.
Developmental, Cognitive, and Behavioral Profile
Some form of developmental delay is almost universally observed in WSS. Delays are commonly seen in both gross and fine motor skills, and in the acquisition of speech and language. The range of intellectual involvement spans from normal cognition to intellectual disability, with most affected individuals falling into the mild-to-moderate intellectual disability range.
A consistent finding in many individuals is that verbal skills may be a relative strength compared to non-verbal skills, such as visual-motor or spatial processing abilities. This uneven cognitive profile can contribute to specific learning challenges, such as greater difficulty with mathematics compared to reading skills.
The behavioral profile associated with WSS is complex and often includes a strong social drive, with many children exhibiting intense sociability and a friendly disposition. Despite this social motivation, individuals often experience behavioral challenges like anxiety, which is frequently reported at clinical levels in both children and adults. Attention deficit issues, similar to those seen in Attention-Deficit/Hyperactivity Disorder (ADHD), are also common.
Some individuals may also exhibit traits associated with Autism Spectrum Disorder (ASD), such as executive dysregulation and a tendency toward restricted or repetitive behaviors. These neurodevelopmental characteristics significantly influence daily life and highlight the need for tailored educational and behavioral supports. Individualized assessment is required to manage anxiety and support cognitive function effectively.
Diagnosis and Ongoing Management Approaches
Diagnosis typically begins with a clinical geneticist or developmental pediatrician recognizing the characteristic combination of physical features and developmental delays. Because WSS features can overlap with those of other genetic syndromes, a definitive diagnosis relies on molecular genetic testing. The most common method today is Whole Exome Sequencing (WES), which analyzes the protein-coding regions of thousands of genes. This testing specifically looks for the pathogenic variant in the KMT2A gene, which confirms the diagnosis.
Management is supportive and symptomatic, focusing on addressing specific health and developmental issues as they arise. There is no cure for the underlying genetic cause, so the goal is to maximize the individual’s function and quality of life.
Care requires a coordinated effort from a multidisciplinary team of specialists. This team often includes:
- A pediatrician
- A clinical geneticist
- A neurologist
- An endocrinologist, particularly if growth hormone deficiency is identified
Early intervention programs are emphasized to support developmental progress, including physical, occupational, and speech therapy. Other common symptomatic treatments involve feeding therapy for early difficulties and addressing gastrointestinal issues like chronic constipation.