Wiedemann-Steiner Syndrome is a rare genetic disorder characterized by a wide array of signs and symptoms, most notably developmental delay, short stature, low muscle tone, and distinctive facial features. Until the advent of advanced genetic testing, it was considered extremely rare, but it is now being diagnosed more frequently.

At its core, WSS is a disorder of epigenetic regulation. This is a complex concept that controls how our genes function.

• A helpful analogy is to think of your DNA as a massive library containing thousands of cookbooks (your genes).
• The recipes in these books do not change, but the library needs a system to control which recipes are used, how often, and at what time. This control system is epigenetics, and it works like a team of librarians using sticky notes and highlighters.
• These epigenetic marks do not change the recipe itself, but they tell the chefs which recipes to read and which ones to ignore.
• In Wiedemann-Steiner syndrome, the genetic mutation affects a master “highlighter pen” , a special enzyme that marks key genes to be turned “on” during development.
• Because this highlighter is broken, it cannot properly mark all the right recipes at the right times. This disrupts numerous developmental processes, from how the bones in the face grow to how the brain makes its connections, leading to the wide-ranging features seen in the syndrome.

In my experience, this syndrome is often suspected when a child presents with global developmental delays and distinct facial features, prompting a genetics referral.

The cause of Wiedemann-Steiner Syndrome is a mutation in the KMT2A gene. The KMT2A gene provides the instructions for making an enzyme that is a type of histone methyltransferase. This enzyme is the “highlighter pen” from our analogy. It works by adding a small chemical mark (a methyl group) to proteins called histones, which are the spools that DNA is wound around. This marking system helps control which genes are accessible and active.

A mutation in this single, master-control KMT2A gene leads to a non-functional enzyme. Without this key epigenetic regulator, the activity of hundreds of other downstream genes is disrupted, leading to the widespread effects on growth, development, and physical features that characterize WSS.

Clinically, I’ve seen that mutations in the KMT2A gene are responsible for this syndrome, the mutation typically occurs spontaneously and is not inherited in most cases.

Wiedemann-Steiner Syndrome is a genetic disorder, but it is almost always a new event within a family. It is not contagious.

• Sporadic (de novo) Mutation: In the vast majority of cases (over 95%), WSS is caused by a de novo mutation. This means that the mutation in the KMT2A gene is a new, random error that occurred by chance during the formation of the egg or sperm cell of a parent, or that happened very early in embryonic development. The parents do not have the mutation, and there is nothing they did or did not do to cause the condition. In these cases, the risk of the parents having another child with WSS is extremely low.
• Autosomal Dominant Inheritance: In very rare cases, the condition can be inherited from a parent who also has WSS. The inheritance pattern is autosomal dominant, which means an affected parent has a 50% chance of passing the condition on to each of their children. This is rare because many individuals with WSS have developmental challenges that may preclude them from having children, and in the past, many mildly affected adults were never diagnosed.

In my experience, I explain to families that this condition is not preventable or caused by anything during pregnancy, it’s a result of a spontaneous change in a gene important for development.

WSS is a spectrum disorder, and the signs and symptoms can vary greatly from person to person. However, there is a constellation of features that are commonly seen.

The most characteristic features include the following:

• Distinctive Facial Features: Many children with WSS share recognizable facial characteristics. These can include long, thick eyelashes; arched, well-defined eyebrows; widely spaced eyes (hypertelorism); downward-slanting eyes; and a broad nasal bridge.
• Hypertrichosis Cubiti (Hairy Elbows): This is a very characteristic, though not universal, sign where there is an unusual amount of hair growth on the outside of the elbows.
• Growth Delay: Many children are born smaller than average, and almost all experience short stature and poor weight gain (“failure to thrive”) in childhood.
• Developmental and Neurological Issues:
  • Developmental Delay: This is a nearly universal feature. Milestones like sitting, crawling, walking, and talking are often significantly delayed.
  • Intellectual Disability: Most individuals have some degree of intellectual disability, which is typically in the mild to moderate range.
  • Hypotonia: Low muscle tone, or “floppiness,” is very common in infancy and can contribute to feeding difficulties and motor delays.
  • Seizures: While not as common as in some other syndromes, seizures can occur.
• Skeletal Abnormalities: A tapered or slender appearance to the ends of the fingers and toes is common.
• Other Medical Issues: Feeding difficulties are very common in infancy. Chronic constipation is also a frequent and challenging problem.

Clinically, I pay attention to both physical traits and behavioral patterns. Some children show features of autism spectrum disorder or ADHD alongside developmental delay.

The diagnostic journey for WSS often involves a long search for answers. The condition is rare and was difficult to diagnose before the era of advanced genetic testing.

• Clinical Suspicion: A diagnosis is often first suspected by a clinical geneticist or a developmental pediatrician who recognizes the combination of developmental delay, short stature, and the characteristic facial features.
• Molecular Genetic Testing: The diagnosis of WSS is definitively confirmed with a molecular genetic test from a blood sample. Because there are many genetic syndromes that cause developmental delay, a doctor will typically order a broad genetic test.
  • Whole Exome Sequencing (WES): This is the most common way WSS is diagnosed today. This powerful test sequences the protein-coding regions of thousands of genes at once. Analysis of the exome data can reveal a new or inherited mutation in the KMT2A gene, confirming the diagnosis.
  • A specific gene panel that includes the KMT2A gene may also be used.
• Comprehensive Evaluation: Once a diagnosis is made, a child will undergo a full evaluation to screen for any associated health problems. This may include a formal developmental assessment, an eye exam, a hearing test, and an evaluation for any feeding or skeletal issues.

Clinically, I use genetic testing (specifically looking for KMT2A mutations) to confirm the diagnosis. Early identification helps guide therapies and resources.

There is no cure for the underlying genetic cause of Wiedemann-Steiner Syndrome. Therefore, management is entirely supportive and symptomatic. The goal is to address the specific medical and developmental challenges each child faces to help them reach their full potential and to support the family. This requires a proactive and coordinated multidisciplinary team.

The key management strategies include:

• Early Intervention and Developmental Therapies: This is the absolute cornerstone of management for a child with WSS. A proactive, intensive therapy program started as early as possible is crucial.
  • Physical Therapy is vital for addressing low muscle tone, improving gross motor skills like sitting and walking, and managing any skeletal issues.
  • Occupational Therapy helps with fine motor skills, sensory processing issues, and learning activities of daily living like feeding and dressing.
  • Speech Therapy is essential for addressing the significant speech and language delays that are common in the syndrome. This may include exploring alternative and augmentative communication (AAC) methods.
• Nutritional Support: In infancy, a feeding therapist and a nutritionist may be needed to manage feeding difficulties and ensure adequate calorie intake for growth. A G-tube may be considered in cases of severe failure to thrive.
• Management of Constipation: This is a common and persistent problem that requires a long-term management plan with a gastroenterologist, often involving dietary changes and laxatives.
• Educational Support: All children with WSS will require an individualized education plan (IEP) at school. A supportive and specialized educational environment is key to helping them learn and succeed.
• Routine Medical Care: Regular follow-up with a pediatrician and other specialists (such as a neurologist if seizures are present) is needed to monitor health and manage any new issues that arise.

I’ve found that supportive therapy like speech, occupational, and physical therapy can greatly improve quality of life, especially when started early.

Wiedemann-Steiner Syndrome is a rare genetic condition that presents a unique set of lifelong challenges related to growth, physical characteristics, and development. The journey for families often begins with a long search for answers, but a definitive genetic diagnosis can provide clarity and a roadmap for the future. While there is no cure that can fix the underlying genetic cause, this does not mean there is no treatment. A proactive, loving, and team-based approach to care can successfully manage the associated health issues and, most importantly, can support a child’s development. Through a strong commitment to early and continuous physical, occupational, and speech therapies, and with the support of a dedicated family and community, children with Wiedemann-Steiner Syndrome can overcome many obstacles and live happy, meaningful lives.

National Organization for Rare Disorders (NORD). (2022). Wiedemann-Steiner Syndrome. Retrieved from https://rarediseases.org/rare-diseases/wiedemann-steiner-syndrome/

National Institutes of Health, Genetic and Rare Diseases Information Center (GARD). (2023). Wiedemann-Steiner syndrome. Retrieved from https://rarediseases.info.nih.gov/diseases/10839/wiedemann-steiner-syndrome

Wiedemann-Steiner Syndrome Foundation. (n.d.). What is WSS?. Retrieved from https://www.wssfoundation.org/