Wolf–Hirschhorn syndrome (WHS) is a

chromosomal deletion syndrome Chromosomal deletion syndromes result from deletion of parts of chromosomes. Depending on the location, size, and whom the deletion is inherited from, there are a few known different variations of chromosome deletions. Chromosomal deletion syndrome ...

resulting from a partial deletion on the short arm of

chromosome 4 Chromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 spans more than 186 million base pairs (the building material of DNA) and represents between 6 and 6.5 percent of the t ...

(del(4p16.3)). 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,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...

Signs and symptoms

The most common characteristics include a distinct craniofacial phenotype (

microcephaly Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...

micrognathia Micrognathism is a condition where the jaw is undersized. It is also sometimes called mandibular hypoplasia. It is common in infants, but is usually self-corrected during growth, due to the jaws' increasing in size. It may be a cause of abnorm ...

, short

philtrum The philtrum ( la, philtrum from Ancient Greek ''phíltron,'' 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 tubercl ...

, prominent

glabella The glabella, in humans, is the area of skin between the eyebrows and above the nose. The term also refers to the underlying bone that is slightly depressed, and joins the two brow ridges. It is a cephalometric landmark that is just superior to ...

, ocular

hypertelorism Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as ...

dysplastic Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic ...

ears and periauricular tags), growth restriction,

, muscle hypotonia, seizures, and congenital heart defects. Less common characteristics include

hypospadias Hypospadias is a common variation in fetal development of the penis in which the urethra does not open from its usual location in the head of the penis. It is the second-most common birth abnormality of the male reproductive system, affecting abou ...

, colobomata of the iris, renal anomalies, and deafness. Antibody deficiencies are also common, including

common variable immunodeficiency Common variable immunodeficiency (CVID) is an immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM and IgA. Symptoms generally include high susceptibility to foreign i ...

and IgA deficiency.

T-cell immunity Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines ...

is normal.

Genetics

Wolf–Hirschhorn syndrome is a

microdeletion syndrome A microdeletion syndrome is a syndrome caused by a chromosomal deletion smaller than 5 million base pairs (5 Mb) spanning several genes that is too small to be detected by conventional cytogenetic methods or high resolution karyotyping (2–5 Mb) ...

caused by a

deletion Deletion or delete may refer to: Computing * File deletion, a way of removing a file from a computer's file system * Code cleanup, a way of removing unnecessary variables, data structures, cookies, and temporary files in a programming language * ...

within HSA band 4p16.3 of the short arm of

, particularly in the region of WHSCR1 and WHSCR2. About 87% of cases represent a ''de novo'' deletion, while about 13% are inherited from a parent with a

chromosome translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...

. 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. 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 Fluorescence ''in situ'' hybridization (FISH) is a molecular cytogenetic technique that uses fluorescent probes that bind to only particular parts of a nucleic acid sequence with a high degree of sequence complementarity. It was developed b ...

(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 Genetic counseling is the process of investigating individuals and families affected by or at risk of genetic disorders to help them understand and adapt to the medical, psychological and familial implications of genetic contributions to disease; t ...

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.

Epidemiology

The minimum birth incidence has been estimated as 1 in 50,000.

History

Wolf–Hirschhorn syndrome was first described in 1961 by the Austrian-born American pediatrician

Kurt Hirschhorn Kurt Hirschhorn (May 18, 1926) - November 25, 2022 was an Austrian-born American pediatrician, medical geneticist, and cytogeneticist who identified the chromosomal defects that underlie Wolf–Hirschhorn syndrome. Early life Hirschhorn was born ...

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