What is Pallister W syndrome?

Pallister W syndrome (PWS), also known as W syndrome, is an extremely rare congenital genetic disorder that is not well-understood. Despite limited research,  scientists have identified consistent patterns that outline how PWS symptoms manifest and affect an individual’s health and development across their lifetime. By using case reports and clinical research, we can establish what is known so far about the long-term outcomes for PWS patients.

Clinical features

A hallmark of PWS is dysmorphic facial features including: cleft lip and palate, broad and flat nasal bridge, broad forehead, acne scarring, downslanted outer edge of the eyes, hypertelorism (an abnormally large distance between the eyes), strabismus (crossed eyes), and lack of upper central incisors. Neurological symptoms are also common, such as: intellectual disability, seizures, speech problems, and hearing impairments. Bone deformities of the extremities are also common. These features may allow a doctor to make a diagnosis, although some symptoms may appear later on in childhood or adulthood. 

Since PWS is extremely rare, only a handful of cases have been reported so there is not a vast amount of literature available outlining the long-term outcomes. However, there is enough research available to identify some patterns in prognosis, symptoms and quality of life. 

Causes

Genetic mutations cause changes in our DNA and these mutations can either be inherited (passed down from parents) or sporadic (new, spontaneous mutations). Pallister W syndrome is thought to be caused by genetic mutations. Although the exact cause of Pallister W syndrome is not known, the disorder is thought to be inherited through an X-linked mutation, meaning that the mutation is located on the X sex-determining chromosome. The syndrome is thought to be an autosomal recessive disorder which means that this disorder can only be passed if both of the parents inherit the same form of the genetic mutation. This is supported by the predominance of affected males (XX sex chromosomes), whereas female patients (XY sex chromosomes) typically exhibit milder symptoms.

At present, no specific causative gene has been confirmed, and reports sometimes describe the inheritance pattern as uncertain. Further research and genetic testing are needed to clarify the underlying genetic cause.

Life over time

The outcomes for PWS patients vary largely and no two individuals with PWS will have the same experiences in their health, ability, or independence. An understanding of how PWS symptoms develop over time may be one of the strongest concerns for families of patients.

Despite the limited data available, some trends in PWS symptom manifestations of PWS are observed

• From infancy to childhood (0-11 years), children with PWS will likely experience developmental delays in cognitive and motor functions, and may not be able to reach certain milestones at the expected time or at all. Dysmorphic facial traits associated with PWS will also manifest in childhood, including a broad forehead, hypertelorism, and a flat nasal bridge. These symptoms may be paired with seizures
• From adolescence to adulthood (12 years and onwards), the symptoms and abilities of each individual are varied. Individuals without major organ problems, such as hearing impairments or bone deformities, often achieve better quality of life, though most patients require  support at this stage. Some learn to walk, talk, and participate in daily activities with little to no assistance, while others remain highly dependent on caregivers

Cognitive development

• Delayed cognitive development usually results in intellectual disability, though its severity typically ranges from mild to moderate. This means that individuals will experience challenges in different aspects of life, but educational support may allow some children to develop academic skills whereas lifelong assistance may be necessary in more severe cases
• Seizures commonly begin adolescence. The type of seizures associated with PWS are bilateral tonic-clonic seizures which can be managed by anti-seizure medicines

Physical development

• Skeletal anomalies such as camptodactyly (permanent flexion of fingers or toes), clinodactyly (permanent curving of fingers or toes), cubitus valgus (outward turned elbows), pes cavus/planus (high-arched foot/flat foot) are described in patients. Although these abnormalities won’t directly shorten life expectancy, they may cause discomfort and limit motor skills. Surgery can repair major deformities of arms and legs if deemed necessary
• Central clefting of the palate and upper lip is frequently observed in affected individuals, but is not exclusive to PWS and is in fact, the most common craniofacial anomaly. The palate separates the nasal and oral cavities which facilitates normal speech production, so clefting results in speech problems. A cleft palate and upper lip may also cause upper jaw malformations and difficulty swallowing and eating. These issues can be addressed and corrected through surgical repair, followed by speech therapy to improve speech post-surgery
• Hearing impairments may also be present in some individuals, though they can be diagnosed quite early on and managed l with hearing aids, cochlear or brainstem implants, signal-to-noise improvement in educational settings, speech therapy, or sign language

Quality of life

As there is no cure for PWS, treatment is focused on managing and minimising symptoms to improve the patient’s quality of life. Patients often have regular check-ups with a multidisciplinary care team which could consist of neurologists to help with seizures, orthopaedic specialists for skeletal issues, audiologists to manage hearing, alongside other healthcare professionals including physical, occupational, and speech therapists. 

Although individuals with PWS and their families face some uncertainty about the long-term outcomes due to a lack of research, it is important to reassure them that with the right interventions, quality of life can be greatly improved. There is often mental health support available for these individuals and their families to cope with the potential stresses. Please contact your local healthcare services to enquire more. 

Genetic counselling may be offered to families even though the mode of inheritance isn’t fully understood yet.

Summary

Pallister W syndrome is a rare, poorly understood and complex disorder. Although outcomes are uncertain, people with PWS are able to live into adulthood with intervention and multidisciplinary support. A better understanding of PWS from more research could inform new interventions to improve long-term outcomes for patients with this condition.