Wolf–Hirschhorn Syndrome
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Wolf–Hirschhorn syndrome (WHS) is a chromosomal deletion syndrome resulting from a partial deletion on the short arm of chromosome 4 el(4)(p16.3) Features include a distinct craniofacial phenotype and
intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...
.


Signs and symptoms

The most common characteristics include a distinct craniofacial phenotype ( microcephaly, micrognathia, short
philtrum The philtrum (, from Ancient Greek , lit. 'love charm') or medial cleft is a vertical indentation in the middle area of the upper lip, common to therian mammals, extending in humans from the nasal septum to the tubercle of the upper lip. Toget ...
, prominent glabella, ocular hypertelorism, dysplastic ears and periauricular tags), growth restriction,
intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...
, muscle hypotonia, seizures, and congenital heart defects. Less common characteristics include
hypospadias Hypospadias is a common malformation in fetal development of the penis in which the urethra does not open from its usual location on the head of the penis. It is the second-most common birth defect of the male reproductive system, affecting about ...
, 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.


Genetics

Wolf–Hirschhorn syndrome is a microdeletion syndrome caused by a deletion within HSA band 4p16.3 of the short arm of chromosome 4, particularly in the region of WHSCR1 and WHSCR2. The phenotypic characteristics of WHS are thought to be caused by the haploinsufficiency of the genes Wolf-Hirschhorn syndrome candidate 1 (WHSC1), which is associated with craniofacial features and growth delay, and Homo Sapiens leucine zipper-EF-hand containing transmembrane protein 1 (LETM1), which is associated with seizures. 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 transmission, there is a 2 to 1 excess of maternal transmission. Of the ''de novo'' cases, 80% are paternally derived. A more uncommon cause for WHS is the formation of a ring chromosome. A ring chromosome can form when a chromosome breaks apart and forms a circular structure to fuse together. That process may initiate gene loss towards the ends of the chromosome. 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 fluorescence in situ hybridization (FISH).
Genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
and genetic counseling is offered to affected families.


Diagnosis

Initial diagnosis is based on a distinct craniofacial phenotype after birth. Diagnosis of WHS is confirmed by the detection of a deletion in the WHSCR. Chromosomal microarray and Cytogenetic analysis.D4S96 or D4Z1 chromosome band 4p16.3–specific probe (Wolf-Hirschhorn region, Vysis, Inc) is available for FISH study.


Treatment

The symptoms can vary from person to person, so the patient should receive different types of evaluations including a neurological, cardiac, and renal evaluation. Eye and hearing exams are essential, as well as a feeding and developmental evaluation. Clinicians treat WHS by addressing the symptoms experienced by the individual. Some treatment methods are surgery for growth abnormalities, educational programs that can help with cognition, physical therapy for muscle building, and medication for seizures.


Epidemiology

The minimum birth incidence has been estimated as 1 in 50,000. For unknown reasons, WHS occurs twice as often in females than in males.


History

Wolf–Hirschhorn syndrome was first described in 1961 by the Austrian-born American pediatrician Kurt Hirschhorn and his colleagues. Thereafter, the syndrome gained worldwide attention after publications by the German geneticist Ulrich Wolf and his co-workers, specifically their articles in the German scientific magazine '' Humangenetik''.


References


External links

* https://www.ncbi.nlm.nih.gov/books/NBK1183/
Wolf-Hirschhorn syndrome
on Genetics Home Reference {{DEFAULTSORT:Wolf-Hirschhorn Syndrome Autosomal monosomies and deletions Rare syndromes Genodermatoses