WSS is a rare, congenital genetic disorder affecting development across multiple body systems. Dr. Hans-Rudolf Wiedemann first described the condition in 1989. WSS is characterized by a distinctive set of physical and developmental features that vary widely among affected individuals. Present from birth, the syndrome affects physical growth and neurological development, leading to a range of challenges.
Defining the Clinical Features
The observable characteristics (phenotype) of WSS are diverse, but certain physical and developmental patterns are commonly reported. Many individuals exhibit distinctive facial features, including widely spaced eyes (hypertelorism) and deep-set eyes with long eyelashes and notably thick or bushy eyebrows.
Another frequently observed physical sign is hypertrichosis, an excess of hair growth often noticeable on the back or elbows. Growth abnormalities are typical, with many children experiencing pre- and postnatal growth restriction resulting in short stature.
Neurological and developmental aspects are consistent features, involving developmental delay and intellectual disability, often classified as mild to moderate. Behavioral issues such as anxiety, hyperactivity, or features of attention-deficit/hyperactivity disorder (ADHD) are also noted.
Challenges often start early, with many infants experiencing feeding difficulties and low muscle tone (hypotonia), which affects motor skill development. Musculoskeletal issues, including minor skeletal changes and anomalies of the hands or spine, are also part of the clinical spectrum.
The Genetic Cause
WSS is directly linked to changes in the $KMT2A$ gene, located on chromosome 11. This gene, previously called $MLL$, provides instructions for a protein that functions as a histone methyltransferase. The $KMT2A$ protein is a master regulator that chemically modifies histones, the proteins that DNA wraps around.
By modifying histones, the $KMT2A$ protein influences the transcription of numerous genes crucial for embryonic and postnatal development. The variants causing WSS are most commonly “loss-of-function” mutations, resulting in a non-working or prematurely terminated protein.
This mechanism leads to haploinsufficiency, where one functional copy of the gene is insufficient for normal development. WSS is an autosomal dominant condition, requiring only one altered copy of the gene. It is typically caused by a de novo mutation, meaning the change is new and not inherited from either parent.
Diagnosis and Supportive Care
Diagnosis begins with clinical suspicion based on the characteristic physical and developmental features. Since the syndrome is rare and variable, definitive diagnosis requires advanced genetic testing. This usually involves molecular analysis, such as whole-exome sequencing, to identify a pathogenic variant in the $KMT2A$ gene.
Management of WSS centers on supportive care, as there is currently no cure for the underlying genetic cause. A coordinated, multidisciplinary team addresses the specific needs of each individual, often including geneticists, pediatricians, neurologists, and developmental therapists.
Therapeutic Interventions
Specific therapies manage developmental delays and physical symptoms. Early intervention programs are highly beneficial. These incorporate physical therapy to address low muscle tone and improve motor skills, and occupational therapy for fine motor skills and daily living activities. Speech therapy is routinely provided for communication delays.
Nutritional support is important, especially for infants experiencing feeding difficulties or failure to thrive, sometimes requiring tube feeding. Ongoing monitoring screens for potential associated medical conditions, such as cardiac, renal, or immunological issues, ensuring prompt treatment of emerging health concerns.