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Pallister–Killian syndrome
A rare chromosomal disorder causing severe developmental delay, hypotonia, and distinctive facial features.
Overview
Pallister–Killian syndrome (PKS) is a rare, sporadic genetic disorder characterized by a wide range of congenital anomalies and developmental disabilities. It results from the presence of an extra isochromosome 12p, leading to mosaic tetrasomy 12p in some cells of the body. The syndrome is named after Drs. Philip Pallister and Wolfgang Killian, who independently described the condition. PKS primarily affects infants and children and is associated with hypotonia (low muscle tone), distinctive facial features, intellectual disability, seizures, pigmentary skin changes, and various structural abnormalities in multiple organ systems. The severity and features can vary depending on the proportion and distribution of abnormal cells in different tissues.
Causes
Pallister–Killian syndrome is caused by the presence of an extra isochromosome 12p, a chromosomal abnormality where there are two extra copies of the short arm of chromosome 12. This results in four copies (tetrasomy) of 12p in affected cells instead of the normal two. The extra chromosome is usually present in a mosaic pattern, meaning only some of the body’s cells contain the abnormal chromosome while others do not. This mosaicism explains the wide variability in clinical presentation. The condition typically arises de novo (sporadically) during early embryonic development and is not inherited from parents.
Symptoms
Individuals with Pallister–Killian syndrome exhibit a broad spectrum of symptoms, which may range from mild to severe. Common features include:
Neurological features: Global developmental delay, intellectual disability, and hypotonia are hallmark features. Seizures may also occur in some cases.
Facial characteristics: Coarse facial features, a high forehead, sparse scalp hair, wide-spaced eyes (hypertelorism), a flat nasal bridge, and a prominent upper lip are commonly seen.
Pigmentary skin anomalies: Areas of hypo- or hyperpigmentation, often following the lines of Blaschko, are frequently present.
Skeletal abnormalities: Include limb shortening, scoliosis, joint contractures, and polydactyly (extra fingers or toes).
Congenital heart defects: A range of structural heart anomalies may be present at birth.
Hearing and vision problems: Sensorineural hearing loss and strabismus (misalignment of the eyes) are common.
Feeding difficulties: Many infants experience poor feeding, gastroesophageal reflux, or require feeding tubes in early life.
Respiratory issues: Breathing problems and a susceptibility to respiratory infections may occur.
Genitourinary anomalies: Kidney malformations or undescended testes in males may be observed.
Diagnosis
Diagnosing Pallister–Killian syndrome requires specialized genetic testing because the abnormal cells may not be detectable in all tissues. The diagnostic process includes:
Clinical evaluation: A thorough assessment of physical features, developmental milestones, and medical history may raise clinical suspicion of PKS.
Cytogenetic testing: Standard karyotyping from blood may be normal due to mosaicism, so skin fibroblast cultures or buccal (cheek) swabs are often used for better detection of the isochromosome 12p.
FISH (Fluorescence in situ hybridization): Can detect low-level mosaicism and confirm the presence of tetrasomy 12p.
Chromosomal microarray or MLPA: May aid in identifying duplications of the 12p arm, especially when conventional methods are inconclusive.
Treatment
There is no cure for Pallister–Killian syndrome. Treatment is symptomatic and supportive, tailored to the individual needs of the patient. A multidisciplinary care team is essential and may include neurologists, cardiologists, geneticists, developmental pediatricians, therapists, and surgeons. Common treatments include:
Early intervention: Physical, occupational, and speech therapies can help improve motor skills, communication, and cognitive development.
Seizure management: Antiepileptic medications are used to control seizures if present.
Surgical interventions: May be required for congenital anomalies such as heart defects, cleft palate, or orthopedic issues.
Feeding support: Feeding therapy and nutritional interventions, including gastrostomy tubes if needed, can address feeding difficulties.
Monitoring and supportive care: Regular follow-up to monitor hearing, vision, growth, and organ function is important.
Educational support: Individualized educational plans (IEPs) are often necessary due to learning difficulties and developmental delay.
Prognosis
The prognosis of Pallister–Killian syndrome varies widely depending on the severity of the symptoms and the extent of mosaicism. Some children may achieve limited developmental milestones, while others remain profoundly delayed. Life expectancy can be reduced in severe cases due to complications from congenital heart defects, respiratory issues, or recurrent infections. However, with early intervention and comprehensive medical support, many individuals can live into adolescence and adulthood. The overall quality of life depends on the degree of functional impairment and the availability of multidisciplinary care and family support.
Medical Disclaimer
The information provided on this page is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.