Pallister-Killian Syndrome

Classification according to ICD-10
Q99.8	Other specified chromosomal abnormalities
ICD-10 online (WHO version 2019)

The Pallister-Killian syndrome , sometimes Teschler-Nicola syndrome or its genetic cause also 12p mosaic tetrasomy called, is named after the doctors who have described first. The syndrome is one of more than 150 described world case studies on rare diseases .

history

In 1977, the American pediatrician and human geneticist Philip D. Pallister first suspected this syndrome in two adults. Independently of this, the Austrian doctor Wolfgang Killian and the human biologist Maria Teschler-Nicola made the same observations on a total of four people in 1981.

genetics

People with a tetrasomy -12p- mosaic have a part of their body cells the short arm (p) of chromosome 12 four times ( tetrasom ) instead of the usual two-fold ( disomic ). These two extra chromosome arms are fused to form a small 47th chromosome, called an isochromosome .

• The isochromosome 12p arises during germ cell maturation in one of the parents by the non- disjunction of two chromosomes 12 and centromere maldivision (transverse division) in one of these two chromosomes, the long arm of which is lost.
• The mosaic arises after fertilization through loss of the isochromosome at an early stage of cell division during the first days of pregnancy.
  Such chromosome changes are not uncommon, but affected children are usually not born alive.

frequency

The exact frequency of Pallister-Killian syndrome is unknown. It occurs sporadically. That is, the likelihood of recurrence in further pregnancies within a family is not increased. One speaks of a " new mutation ". In 2010, there were 38 known children with Pallister-Killian syndrome between 0 and 22 years in Germany and the surrounding countries. It is assumed that there are other affected children, adolescents or adults as well.

pregnancy

The pregnancy is generally unremarkable. The children are usually born on the date and have the usual birth measurements. However, the effects of tetrasomy 12p are serious: the children stand out from the start with their unusual appearance. Their pigment changes sometimes lead to the diagnosis (see below). Often there are organ malformations or certain organ functions are restricted. Motor development is very slow. Little is known about the cognitive potential. Most children are considered to be severely cognitively disabled . In fact, in recent times, those affected have been provided with modern technology such as B. opened up new communication channels with eye-controlled PCs.

Symptoms

The most common symptoms of Pallister-Killian syndrome are:

• Muscular hypotension (very flaccid muscle tone due to brain dysfunction), as a result of which the erectile function is severely delayed
• long face with a bulging forehead , upward sloping (laterally-cranially rising) lid axes , broad nasal root and a conspicuous mouth region
• high palate
• thinning hair , especially around the temples
• uneven pigment distribution on the torso, arms or legs; the skin looks blotchy, especially in summer
• severe linguistic development delay up to the absence of spoken language ; however, children's speech understanding is unlikely to be impaired, provided their hearing is normal.
  In addition, the following can occur:
• excess fingers or toes
• epileptic seizures ; they often appear for the first time in toddlerhood and are sometimes difficult to adjust
• Inner ear hearing loss
• Visual impairment
• Heart defect
• Misaligned teeth
• Diaphragmatic hernia
• Malformations and tumors on the kidneys
• Malformations of the genitals
  • in boys: undescended testicles, small scrotum
  • In girls: atrophied labia majora , unpaired genitals, misalignments of the vagina or uterus
• Absence of the 12th pair of ribs .

Because of their weak muscles, the spine of many children bends in the course of their growth ( scoliosis ). This can be so pronounced that an operative straightening is necessary. A fusion of the cervical vertebrae ( block vertebrae ) is less common .

Children with Pallister-Killian syndrome are prone to infection . They often have problems with eating; some do not learn to chew and bite. Due to their motor impairments, they can show little initiative and do little without support. Their interest in the environment appears to be low, but this is not accompanied by any social conspicuousness. They need intensive physical help and care for life. Just as important for them are spiritual stimuli so that they do not become impoverished, lonely and develop stereotypes in their social environment .
Many older people with Pallister-Killian syndrome are short for their age ( short stature ). Life expectancy depends on their organs. There have been reports of adults over 40 years of age. It appears that boys with Pallister-Killian syndrome have better motor development opportunities than girls.

forecast

Since the Pallister-Killian syndrome is a chromosome mosaic, i.e. the surplus isochromosome 12p is not present in all body cells, no exact statements can be made about the available development potential after the chromosome diagnosis. A direct connection between the proportion of cells with tetrasomy 12p in the child's organism and the severity of the syndrome is assumed. However, the examination of individual tissues does not allow any conclusions to be drawn about the distribution of the two cell lines throughout the body.

Diagnosis

The diagnosis of Pallister-Killian syndrome can be difficult. Routine chromosome analyzes from blood cells usually show a normal set of chromosomes. The tetrasome cell line is mostly detected in cultured skin cells. For this, some skin must be removed from the children ( skin biopsy ). Diagnostics with fluorescence-labeled probes on oral mucous membrane cells is now also possible. In the prenatal chromosomal diagnosis to an existing tetrasomy can not always prove 12p mosaic. The antenatal diagnosis of Pallister-Killian syndrome depends on whether or not there are tetrasome cells in the tissue sample being examined. A child with Pallister-Killian syndrome can be born even after an unremarkable result of the chromosome examination on amniotic fluid cells ( amniocentesis ).

Differential diagnosis

The Fryns syndrome must be distinguished .

See also

• List of syndromes

Individual evidence

1. ↑ orpha.net
2. ^ Genetics Home Reference: Pallister-Killian mosaic syndrome. Retrieved March 6, 2020 . 

Web links

• Tetrasomy 12p at orpha.net

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !