Pallister Killian Syndrome

What is Pallister Killian Syndrome?

The Pallister Killian syndrome is a condition in which 12 chromosome has four copies of the short arms instead of two in normal numbers. The outcome of this condition leads to developmental disorder during infancy and early childhood due to exceptionally weak muscle tone. Other congenital disorders include atypical facial appearance, less hair growth, pigmented skin, intellectual disability.

Inherited involvement does not associate with the Pallister-Killian mosaic syndrome, but during or after fertilization disorder develops and causes genetic defects. Decreased strength and energy level in the child leads to breathing difficulty, feeding problem etc.

Alternatively, Pallister Killian syndrome is also known as Hexasomy 12p, Mosaic; Pallister Mosaic Syndrome Tetrasomy 12p or Killian Syndrome^1,2.

Symptoms

The symptoms of Pallister Killian syndrome vary depending upon, which tissue has additional chromosomal materials; the symptoms also unevenly distributed at each side. Following symptoms are included in Pallister Killian Syndrome:

Atypical Facial Features

• Prominent forehead,
• Facial skin is coarser,
• Wide spaced eyes
• Broad nasal bridge
• Extremely arched palate
• A folded skin over the inner angle of the eyes
• Thick and protrude outward large ears lobes
• Thin hair density on the scalp

Muscular abnormality

• Congenital hypotonia (low muscle tone)
• Feeding difficulty, breathing problem, walking and standing disorders due to congenital hypotonia. Almost 70 percent of the affected individuals unable to walk properly and require additional support to walk.

Mental disorders

Delayed perceiving, impediment reorganization, intellectual disability are mostly noticeable to all Pallister Killian Syndrome affected individuals. Cognitive impairments causes lack of judging, imagination and reasoning power, lack of sensing ability, speech problem and hearing loss.

Other abnormalities

Some other Pallister Killian Syndrome associated abnormalities are congenital cardiac problems, hernias or protrude off the diaphragm, stenosis or external auditory canal contraction and an anomalous opening in the anus. Some infants affected with Pallister Killian Syndrome may have a hypoplastic (underdeveloped) lung, genitourinary abnormality, and skeletal malformations^1,3,4.

Causes

Instead of normal two copies of gene existence of four copies of the short arm of chromosome 12 causes the Pallister Killian syndrome. The additional two chromosomal units at 12p appear as isochromosome (single unit), but this type of involvement is not associated with every cell of the body. Therefore the term mosaicism is used. Pallister Killian syndrome is restricted to certain cells.

However, yet now prenatal diagnosis is not possible to determine the cellular involvement of this type of chromosomal symptoms. The extra chromosomal material presence in the cells causes normal genetic disruption and resultant of this leads to arising of signs and symptoms of Pallister Killian syndrome. During the fertilization in the mother womb, the fetus gets affected and cause erotic cell division and resultant of that leads to Pallister Killian syndrome⁴.

Genetic Involvement

In Pallister Killian syndrome, a 12p region of the chromosome gets affected and lie between p arm terminated part and at the band 12.3. In this region almost 300 genes are present and alteration of one gene expression leads to consequent alteration of the other associated genes and chromosomes. A recent study conducted on fibroblast cells sample collected from Pallister Killian syndrome affected individuals reported that gene expression altered at the region of 12p13.31 and 354 genes had changed expression².

Diagnosis

DNA examination conducted by taking a sample from white blood cells usually used to detect chromosomal disorders. But Pallister Killian syndrome affected children have normal blood cells chromosomes. Therefore, the mostly sample is collected from skin cells, or from buccal mucosa (inside the cheeks).

The sample is diagnosed under karyotyping method, in which the number of chromosomes is counted. Array comparative genomic hybridization or fluorescence in situ hybridization are the techniques available for close monitoring of the chromosomes for detail analysis.

The usual findings after analyzing the chromosomes are instead of normal 46 chromosomes, 47 chromosomes are identified on the affected individuals. The extra chromosome does not contain any long arm (q), but two short arms (p)^1,2,5.

Treatment

There is no curable treatment available for Pallister Killian Syndrome. The treatment approach of the Pallister Killian Syndrome is to provide symptomatic relief and to avoid further complications. The following are the different therapeutic measures apply to the Pallister-Killian Syndrome affected individuals depending upon the patient’s condition:

• Application of breathing aid during the respiratory complications
• Surgical intervention requires for correction for a diaphragmatic hernia.
• Poor eyesight can be treated by the different optical device or surgical corrective intervention.
• Surgical interventions or braces are applied to treat and repair abnormal curvature of the verbal column.
• Cardiac surgery requires treating heart problem
• Limb abnormalities require to surgical intervention
• Anti-epileptic drugs are given to the patients for control convulsion
• Different supportive aids and therapy applied depending upon the delayed developmental symptoms
• Regular follow-up therapy is very important to monitor the patient conditions. Any symptomatic worsening causes immediate medical attention to restricting the complication⁴.

Prognosis & Life Expectancy

Pallister Killian Syndrome life expectancy is not uniform, as it associated with multiple developmental abnormalities. depending on the severity of the symptoms and complications life expectancy may not be prolonged for affected individuals. Most of the defects are congenital, therefore, it is difficult to estimate the severity of the outcome of the syndrome.

The sign and severity of the Pallister Killian Syndrome are progressive and that extend from infancy to childhood and adulthood. After the birth of the Pallister Killian Syndrome affected neonates mostly require intensive care, because of breathing difficulties. If neonates survive during their infancy, most of the cases they require lifelong medication and supportive care to survive¹.

References

1. Pallister Killian Syndrome, (2016); DoveMed; Retrieve from http://www.dovemed.com/diseases-conditions/pallister-killian-syndrome-pks/
2. Pallister Killian syndrome; Rare Chromosome Disorder Support Group; Retrieve from http://www.rarechromo.org/information/Chromosome%2012/Pallister-Killian%20syndrome%20FTNP.pdf
3. Pallister Killian syndrome; Med Genet 1991; 28: 122-125 Downloaded from http://jmg.bmj.com/ on April 2, 2017 – Published by group.bmj.com; Retrieve from http://jmg.bmj.com/content/jmedgenet/28/2/122.full.pdf
4. Pallister Killian Mosaic Syndrome; National Organization for Rare Disorders; Retrieve from https://rarediseases.org/rare-diseases/pallister-killian-mosaic-syndrome/
5. Pallister-Killian mosaic syndrome; Genetic Home References; Retrieve from https://ghr.nlm.nih.gov/condition/pallister-killian-mosaic-syndrome#diagnosis