Pallister-Killian syndrome (Pallister mosaic syndrome, Killian/Teschler-Nicola syndrome, Tetrasomy 12p)

Pallister-Killian syndrome (Pallister mosaic syndrome, Killian/Teschler-Nicola syndrome, tetrasomy 12p) is a rare genetic condition. It is generally a sporadic condition, with no established pattern of inheritance; therefore, absence of a relevant family history would be expected. The chromosomal abnormality is mosaic, meaning that it is present in some cells of the body but not others, and the proportion of affected cells can vary between tissues. A distinctive presentation may include the combination of severe intellectual disability and seizures, hypotonia, a long philtrum with a thin upper lip and distinct Cupid's-bow configuration, temporal alopecia, and streaks of hypo- and hyperpigmentation.

It can present with psychiatric features such as behavioural dysregulation, irritability, aggression and self-injurious behaviour. Behavioural difficulties may occur in the context of severe intellectual disability and communication impairment. The neurodevelopmental manifestations generally emerge in infancy or early childhood, and late-onset psychiatric presentations in adulthood are not characteristic.

From a morphologic lens perspective, other features include (but are not limited to):

• Prominent forehead

• Widely spaced eyes

• Downslanted palpebral fissures

• Low-set ears

• Broad nasal bridge

• Short nose

• Long philtrum

• Wide mouth

• Large tongue

• Polydactyly

• Clinodactyly of fifth fingers

Other characteristic features include congenital hypotonia, severe developmental delay and intellectual disability, with significant speech and language impairment. Neurological manifestations include seizures, abnormal muscle tone and motor impairment; structural brain abnormalities may include ventriculomegaly, abnormalities of the corpus callosum, cerebral atrophy and cortical malformations such as polymicrogyria. Characteristic skin abnormalities include areas of hypo- or hyperpigmentation, often with a streaky or whorled distribution. Other congenital abnormalities can include diaphragmatic hernia, omphalocele, congenital heart defects, renal and genitourinary abnormalities, gastrointestinal abnormalities including anal atresia, hearing impairment and ophthalmological abnormalities. Skeletal manifestations may include rhizomelia, short hands and feet, clinodactyly, syndactyly and scoliosis. Feeding difficulties and failure to thrive are common, particularly in infancy. Macrosomia at birth may occur, and the severity of the phenotype is highly variable, ranging from severe multisystem congenital disease to individuals with milder developmental impairment.

Early diagnosis is important to identify and manage seizures, hypotonia and other neurological complications; recognise congenital cardiac, respiratory, gastrointestinal, renal and genitourinary abnormalities; assess hearing, vision and developmental needs; facilitate appropriate genetic counselling and family assessment; and recognise that a normal blood chromosome analysis does not exclude the diagnosis, because the mosaic chromosomal abnormality may be absent from peripheral blood cells and detectable only in other tissues.