Wolf-Hirschhorn syndrome
Encyclopedia
Wolf–Hirschhorn syndrome (WHS), also known as chromosome deletion 4p syndrome, Pitt-Rogers-Danks syndrome (PRDS) or Pitt syndrome, was first described in 1961 by Americans Herbert L. Cooper and Kurt Hirschhorn
and, thereafter, gained worldwide attention by publications by the German Ulrich Wolf, and Hirschhorn and their co-workers, specifically their articles in the German scientific magazine Humangenetik. It is a characteristic phenotype resulting from a partial deletion of chromosomal material of the short arm of chromosome
4 (del(4p16.3)).
The most common characteristics include a distinct craniofacial phenotype (microcephaly
, micrognathia, short philtrum, prominent glabella, ocular hypertelorism
, dysplastic ears and periauricular tags), growth and mental retardation, muscle hypotonia, seizures, and congenital heart defects. Less common characteristics include hypospadias
, colobomata of the iris, renal anomalies, and deafness. Antibody deficiencies are also common, including common variable immunodeficiency
and IgA deficiency. T-cell immunity is normal.
4, particularly in the region of and . About 87% of cases represent a de novo deletion, while about 13% are inherited from a parent with a chromosome translocation
. In the cases of familial translocation, there is a 2 to 1 excess of maternal transmission. Of the de novo cases, 80% are paternally derived. Severity of symptoms and expressed phenotype differ based on the amount of genetic material deleted. The critical region for determining the phenotype is at 4p16.3 and can often be detected through genetic testing and fluorescent in situ hybridization (FISH). Genetic testing
and genetic counseling
is offered to affected families.
Kurt Hirschhorn
Kurt Hirschhorn , is an Viennese born American pediatrician, medical geneticist, and cytogeneticist who identified the chromosomal defects that underlie Wolf-Hirschhorn syndrome....
and, thereafter, gained worldwide attention by publications by the German Ulrich Wolf, and Hirschhorn and their co-workers, specifically their articles in the German scientific magazine Humangenetik. It is a characteristic phenotype resulting from a partial deletion of chromosomal material of the short arm of chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
4 (del(4p16.3)).
Signs and symptoms
Microcephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
, micrognathia, short philtrum, prominent glabella, ocular 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...
, dysplastic ears and periauricular tags), growth and mental retardation, muscle hypotonia, seizures, and congenital heart defects. Less common characteristics include hypospadias
Hypospadias
Hypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus...
, colobomata of the iris, renal anomalies, and deafness. Antibody deficiencies are also common, including common variable immunodeficiency
Common variable immunodeficiency
Common variable immunodeficiency is a group of approximately 150 primary immunodeficiencies , which have a common set of symptoms but which have different underlying causes.Common variable immunodeficiency is the most commonly encountered primary immunodeficiency.-Causes and types:CVID...
and IgA deficiency. T-cell immunity is normal.
Genetics
Wolf-Hirshhorn syndrome is caused by a partial deletion of the short arm of chromosomeChromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
4, particularly in the region of and . About 87% of cases represent a de novo deletion, while about 13% are inherited from a parent with a chromosome translocation
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
. In the cases of familial translocation, there is a 2 to 1 excess of maternal transmission. Of the de novo cases, 80% are paternally derived. Severity of symptoms and expressed phenotype differ based on the amount of genetic material deleted. The critical region for determining the phenotype is at 4p16.3 and can often be detected through genetic testing and fluorescent in situ hybridization (FISH). Genetic testing
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
and genetic counseling
Genetic counseling
Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...
is offered to affected families.
External links
- WolfHirschhorn.org
- Wolf-Hirschhorn syndrome at www.orpha.net (Adobe .pdf format)
- 4P- Support Group
- Wolf Hirschhorn Syndrome Trust for the UK and Ireland