Pallister-Killian syndrome
Encyclopedia
Pallister–Killian syndrome (also tetrasomy 12p mosaicism or Pallister mosaic aneuploidy syndrome) is an extremely rare genetic disorder
occurring in human
s. Pallister-Killian occurs due to the presence of the anomalous extra isochromosome
12p, the short arm of the twelfth chromosome
. This leads to the development of tetrasomy
12p. Because not all cells have the extra isochromosome, Pallister-Killian is a mosaic
condition.
It was first described by Philip Pallister in 1977 and further researched by Maria Teschler-Nicola and W. Killian in 1981.
, epilepsy
, hypotonia
, and both hypopigmentation
and hyperpigmentation
. Patients also exhibit a distinctive facial structure, characterized by high foreheads, sparse hair on the temple, a wide space between the eyes, epicanthal fold
s, and a flat nose. Visual impairments and deafness may occur. Patients may also exhibit congenital heart defects, gastroesophageal reflux
, cataract
s, and supernumerary nipple
s. Diaphragm
problems seen in newborns can lead to death shortly after birth.
As patients pass into adolescence, the syndrome is characterized by a coarse and flat face, macroglossia
prognathia, inverted lower lip, and psychomotor retardation
with muscular hypertonia
and contracture
s.
, both maternally and paternally. Several theories regarding to mechanism of this formation have been introduced.
and amniotic fluid
cell samples. Very rarely, it can also be detected in blood lymphocyte
s. 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.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
occurring in human
Human
Humans are the only living species in the Homo genus...
s. Pallister-Killian occurs due to the presence of the anomalous extra isochromosome
Isochromosome
An isochromosome is a chromosome that has lost one of its arms and replaced it with an exact copy of the other arm. This is sometimes seen in some females with Turner syndrome or in tumor cells. This may also cause an isochromosome to have two centromeres The chromosome arm is already copied during...
12p, the short arm of the twelfth chromosome
Chromosome 12 (human)
Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 143 million base pairs and represents between 4 and 4.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
. This leads to the development of tetrasomy
Tetrasomy
A tetrasomy is a form of aneuploidy with the presence of four copies, instead of the normal two, of a particular chromosome.-Full:Full tetrasomy of an individual occurs due to non-disjunction when the cells are dividing to form egg and sperm cells . This can result in extra chromosomes in a sperm...
12p. Because not all cells have the extra isochromosome, Pallister-Killian is a mosaic
Mosaic (genetics)
In genetic medicine, a mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one individual who has developed from a single fertilized egg...
condition.
It was first described by Philip Pallister in 1977 and further researched by Maria Teschler-Nicola and W. Killian in 1981.
Characteristics
Characteristics include varying degrees of developmental disabilityDevelopmental disability
Developmental disability is a term used in the United States and Canada to describe lifelong disabilities attributable to mental or physical impairments, manifested prior to age 18. It is not synonymous with "developmental delay" which is often a consequence of a temporary illness or trauma during...
, epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
, hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
, and both hypopigmentation
Hypopigmentation
Hypopigmentation is the loss of skin color. It is caused by melanocyte or melanin depletion, or a decrease in the amino acid tyrosine, which is used by melanocytes to make melanin.-Treatments:...
and hyperpigmentation
Hyperpigmentation
In dermatology, hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.-Causes:Hyperpigmentation may be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris...
. Patients also exhibit a distinctive facial structure, characterized by high foreheads, sparse hair on the temple, a wide space between the eyes, epicanthal fold
Epicanthal fold
An epicanthic fold, epicanthal fold, or epicanthus is a skin fold of the upper eyelid, covering the inner corner of the eye....
s, and a flat nose. Visual impairments and deafness may occur. Patients may also exhibit congenital heart defects, gastroesophageal reflux
Gastroesophageal reflux disease
Gastroesophageal reflux disease , gastro-oesophageal reflux disease , gastric reflux disease, or acid reflux disease is chronic symptoms or mucosal damage caused by stomach acid coming up from the stomach into the esophagus...
, cataract
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
s, and supernumerary nipple
Supernumerary nipple
A supernumerary nipple is an additional nipple occurring in mammals, including humans...
s. Diaphragm
Thoracic diaphragm
In the anatomy of mammals, the thoracic diaphragm, or simply the diaphragm , is a sheet of internal skeletal muscle that extends across the bottom of the rib cage. The diaphragm separates the thoracic cavity from the abdominal cavity and performs an important function in respiration...
problems seen in newborns can lead to death shortly after birth.
As patients pass into adolescence, the syndrome is characterized by a coarse and flat face, macroglossia
Macroglossia
Macroglossia is the medical term for unusual enlargement of the tongue. Severe enlargement of the tongue can cause cosmetic and functional difficulties including in speaking, eating, swallowing and sleeping.- Amyloid Disorders :...
prognathia, inverted lower lip, and psychomotor retardation
Psychomotor retardation
Psychomotor retardation involves a slowing-down of thought and a reduction of physical movements in an individual. Psychomotor retardation can cause a visible slowing of physical and emotional reactions, including speech and affect...
with muscular hypertonia
Hypertonia
Hypertonia a condition marked by an abnormal increase in muscle tension and a reduced ability of a muscle to stretch. It is caused by lesions to upper motor neurons in the central nervous system, which carry information from the central nervous system to the muscles and control posture, muscle...
and contracture
Contracture
A muscle contracture is a permanent shortening of a muscle or joint.. It is usually in response to prolonged hypertonic spasticity in a concentrated muscle area, such as is seen in the tightest muscles of people with conditions like spastic cerebral palsy....
s.
Causes
Pallister-Killian does not appear to be hereditary. Some research has suggested that the presence of the extra chromosome may be linked to premeiotic mitotic errorsNondisjunction
Nondisjunction is the failure of chromosome pairs to separate properly during meiosis stage 1 or stage 2. This could arise from a failure of homologous chromosomes to separate in meiosis I, or the failure of sister chromatids to separate during meiosis II or mitosis. The result of this error is a...
, both maternally and paternally. Several theories regarding to mechanism of this formation have been introduced.
Diagnosis
The isochromosome can be primarily detected in samples of skin fibroblasts, as well as in chorionic villusChorionic villi
Chorionic villi are villi that sprout from the chorion in order to give a maximum area of contact with the maternal blood.Embryonic blood is carried to the villi by the branches of the umbilical arteries, and after circulating through the capillaries of the villi, is returned to the embryo by the...
and amniotic fluid
Amniotic sac
The amniotic sac is the sac in which the fetus develops in amniotes. It is a tough but thin transparent pair of membranes, which hold a developing embryo until shortly before birth. The inner membrane, the amnion, contains the amniotic fluid and the fetus. The outer membrane, the Chorion,...
cell samples. Very rarely, it can also be detected in blood lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s. 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
Hypertelorism
Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits . In this condition the distance between the inner eye corners as well as the distance between the pupils is greater than normal...
, broad neck, shorts limbs, abnormal hands or feet, diaphragmatic hernia
Hernia
A hernia is the protrusion of an organ or the fascia of an organ through the wall of the cavity that normally contains it. A hiatal hernia occurs when the stomach protrudes into the mediastinum through the esophageal opening in the diaphragm....
, and hydramnios
Polyhydramnios
Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in 0.2 to 1.6% of pregnancies,,...
. Once born, a child may be diagnosed by observation of the syndrome's distinct facial features.