Pallister-Killian Syndrome

Pallister-Killian syndrome is a sporadic chromosomal disorder due to mosaic tetrasomy of 12p, usually from a supernumerary isochromosome 12p. It causes coarse facial features, sparse hair, pigmentary skin changes, severe intellectual disability, hypotonia and often congenital diaphragmatic hernia.

Pathophysiology. A post-zygotic error in meiosis or early mitosis leads to an extra isochromosome 12p, giving four copies of the short arm in some cells. The proportion of abnormal cells differs between tissues, and it is higher in skin fibroblasts and amniocytes than in blood.

The abnormal cell line is often lost from blood with age.

Because blood karyotypes are frequently normal, tissue testing is needed.

• Coarse face with a prominent forehead, sparse frontotemporal hair, a broad nasal bridge, a long philtrum, and a thin upper lip
• Pigmentary streaks and patches of skin
• Congenital diaphragmatic hernia in about 20%, with pulmonary hypoplasia
• Severe intellectual disability, absent or limited speech
• Hypotonia in infancy, later spasticity or joint contractures
• Seizures (infantile spasms, myoclonic and tonic clonic seizures)
• Sensorineural or conductive hearing loss
• Congenital heart disease, genital anomalies, and anal anomalies
• Short neck, extra nipples, and rhizomelic limb shortening
• Feeding difficulty and reflux
• Cataracts and strabismus in some

• Karyotype or FISH of skin fibroblasts, buccal cells or other tissue, because blood karyotype is often normal.
• Chromosomal microarray on DNA from buccal cells or skin to detect 12p gain, with reduced sensitivity in blood.
• Prenatal diagnosis: amniocentesis (karyotype or array) in a pregnancy with a diaphragmatic hernia or coarse features on ultrasound.
• Echocardiography, renal ultrasound, hearing assessment and ophthalmology review.
• EEG and brain MRI when seizures or regression occur.

• Diaphragmatic hernia: postnatal stabilisation with gentle ventilation and surgical repair when stable, with long term respiratory follow up.
• Seizures: for infantile spasms give vigabatrin 50 mg/kg daily increasing to 100 to 150 mg/kg daily, or prednisolone 40 to 60 mg daily for 14 days. For other seizures give levetiracetam 10 mg/kg twice daily increasing to 30 mg/kg twice daily, or valproate 10 mg/kg twice daily increasing to 20 mg/kg twice daily. Provide a rescue plan: buccal midazolam 0.3 mg/kg (maximum 10 mg) for a seizure lasting over 5 minutes.
• Feeding and reflux: feeding therapy, gastrostomy for unsafe swallow, and omeprazole 0.7 to 1 mg/kg daily.
• Hearing: grommets or hearing aids, and yearly audiology.
• Eye care: cataract surgery when vision is affected, and strabismus treatment.
• Musculoskeletal care: physiotherapy and orthotics for contractures and spasticity, with baclofen 0.3 mg/kg daily in divided doses increasing weekly to 2 mg/kg daily (maximum 60 mg) if needed.
• Cardiac and genitourinary care: repair of significant defects.
• Development and communication: early intervention, augmentative communication and special education.
• Genetic counselling: the recurrence risk is very low because the change arises after fertilisation.

Special groups.

• Pregnancy with a diaphragmatic hernia and coarse features: offer amniotic fluid testing, because blood from the foetus may be normal.

Monitoring. Growth, feeding and respiratory status every 3 months in infancy. Seizures and development every 6 months, and hearing and eye review yearly.

Referral and escalation. Refer to clinical genetics, paediatric surgery, neurology and audiology. Emergency for respiratory distress, prolonged seizures or aspiration.