Pallister-Killian mosaic syndrome

Alternate names

Chromosome 12, Isochromosome 12p syndrome; Killian syndrome; Killian Teschler-Nicola syndrome; Pallister mosaic syndrome; Teschler-Nicola Killian syndrome; Tetrasomy 12p, mosaic; Pallister Killian syndrome; PKS

Definition

Pallister-Killian mosaic syndrome is a multi-system disorder that is characterized by extremely weak muscle tone (hypotonia) in infancy and early childhood, intellectual disability, distinctive facial features, sparse hair, areas of unusual skin coloring (pigmentation), and other birth defects.

Epidemiology

• Pallister-Killian mosaic syndrome appears to be a rare condition, although its exact prevalence is unknown.
• This disorder may be underdiagnosed because it can be difficult to detect in people with mild signs and symptoms.
• As a result, most diagnoses are made in children with more severe features of the disorder.
• More than 150 people with Pallister-Killian mosaic syndrome have been reported in the medical literature.

Cause

• Pallister-Killian mosaic syndrome is usually caused by the presence of an abnormal extra chromosome called an isochromosome 12p or i(12p).
• An isochromosome is a chromosome with two identical arms. Normal chromosomes have one long (q) arm and one short (p) arm, but isochromosomes have either two q arms or two p arms.
• Isochromosome 12p is a version of chromosome 12 made up of two p arms.
• Cells normally have two copies of each chromosome, one inherited from each parent. In people with Pallister-Killian mosaic syndrome, cells have the two usual copies of chromosome 12, but some cells also have the isochromosome 12p.
• These cells have a total of four copies of all the genes on the p arm of chromosome 12.
• The extra genetic material from the isochromosome disrupts the normal course of development, causing the characteristic features of this disorder.
• Although Pallister-Killian mosaic syndrome is usually caused by the presence of an isochromosome 12p, other, more complex chromosomal changes involving chromosome 12 are responsible for the disorder in rare cases.

Inheritance

• Pallister-Killian mosaic syndrome is not inherited.
• The chromosomal change responsible for the disorder typically occurs as a random event during the formation of reproductive cells (eggs or sperm) in a parent of the affected individual, usually the mother.
• Affected individuals have no history of the disorder in their families.
• An error in cell division called nondisjunction likely results in a reproductive cell containing an isochromosome 12p.
• If this atypical reproductive cell contributes to the genetic makeup of a child, the child will have two normal copies of chromosome 12 along with an isochromosome 12p.
• As cells divide during early development, some cells lose the isochromosome 12p, while other cells retain the abnormal chromosome.
• This situation is called mosaicism.
• Almost all cases of Pallister-Killian mosaic syndrome are caused by mosaicism for an isochromosome 12p.
• If all of the body's cells contained the isochromosome, the resulting syndrome would probably not be compatible with life.

Signs and symptoms

The signs and symptoms of Pallister-Killian mosaic syndrome can vary, although most documented cases of people with the syndrome have severe to profound intellectual disability and other serious health problems.

Signs and symptoms

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Cachexia(Wasting syndrome)
• Delayed eruption of teeth(Delayed eruption)
• Delayed skeletal maturation(Delayed bone maturation)
• Downturned corners of mouth(Downturned corners of the mouth)
• Everted lower lip vermilion(Drooping lower lip)
• Hypohidrosis(Decreased ability to sweat)
• Intellectual disability, severe(Early and severe mental retardation)
• Joint hyperflexibility(Joints move beyond expected range of motion)
• Long philtrum
• Muscular hypotonia(Low or weak muscle tone)
• Ptosis(Drooping upper eyelid)
• Reduced tendon reflexes
• Short neck(Decreased length of neck)
• Short stature(Decreased body height)
• Sparse and thin eyebrow(Thin, sparse eyebrows)
• Sparse hair
• Thick upper lip vermilion(Full upper lip)
• Thin upper lip vermilion(Thin upper lip)

30%-79% of people have these symptoms

• Anteverted nares(Nasal tip, upturned)
• Coarse facial features(Coarse facial appearance)
• Frontal bossing
• Hypertelorism(Wide-set eyes)
• Prominent forehead(Pronounced forehead)
• Short nose(Decreased length of nose)
• Telecanthus(Corners of eye widely separated)
• Upslanted palpebral fissure(Upward slanting of the opening between the eyelids)

5%-29% of people have these symptoms

• Abnormal soft palate morphology
• Anal atresia(Absent anus)
• Strabismus(Cross-eyed)

Diagnosis

• The isochromosome i(12p) can be primarily detected in samples of skin fibroblasts, as well as in chorionic villus and amniotic fluid cell samples. Very rarely, it can also be detected in blood lymphocytes.
• It is also possible to detect the isochromosome in circulating lymphocytes, as well as other amniotic and placental samples.
• There is no strict limit as to where the isochromosome can be found.
• However, it is often unlikely that these samples will be tested when the blood karyotype is normal.
• Using an ultrasound, Pallister–Killian may be diagnosed through observation of hypertelorism, broad neck, shorts limbs, abnormal hands or feet, diaphragmatic hernia, and hydramnios.
• Once born, a child may be diagnosed by observation of the syndrome's distinct facial features.

Treatment

Treatment depends upon the specific symptoms present in each individual. Treating medical and developmental problems early can help to optimize outcome.

NIH genetic and rare disease info

• NIH info on Pallister-Killian mosaic syndrome

Pallister-Killian mosaic syndrome is a rare disease.

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