Genetic mutations: Wolf-Hirschhorn syndrome

Wolf-Hirschhorn syndrome (4p16.3 deletion)

Wolf Hirschhorn syndrome or 4p- is a rare developmental disease characterized by multiple congenital anomalies and mental retardation. An incidence of 1 per estimated 50,000 newborns. It is characterized by a peculiar shaped face Greek helmet, microcephaly, cranial asymmetry, hypertelorism, bilateral coloboma, retrognathia, carp-shaped mouth, dysplastic and low-set ears, seizures with usually 9-10 months early start, congenital heart disease (which is present from birth): aortic coarctation, atrial and ventricular septal defect, incurvado penis, hypospadias, renal hypoplasia or absence in less than 10% of cases and mental retardation.

Physical signs and symptoms

·         Its main features are:

·         Typical childhood craniofacial features consisting of "short Greek warrior helmet appearance of the nose (the bridge of the nose continues on the wide front), microcephaly, high forehead with prominent glabella, ocular hypertelorism, epicanthal folds, highly arched eyebrows, filtrum , mush mouth, micrognathia and malformed ears with pits / tags.

·         All affected individuals have prenatal onset growth deficiency followed by postnatal growth retardation and underdevelopment with muscular hypotonia.

·         The developmental delay or intellectual disability is present to varying degrees in all.

·        Seizures occur between 50% and 100% of children with SWH.

·         Other findings include skeletal abnormalities (60% -70%), congenital heart defects (~ 50%), hearing loss (mostly drivers) (> 40%), urinary tract malformations (25%), and structural brain abnormalities (33%).

·         Low birth weight.

·         Muscle tone at birth.

·         Small head (microcephaly).

·         Skull with asymmetry.

·         Lip and cleft palate (cleft lip) in 50% of patients.

·         Distinctive face; Greek helmet shaped.

·         Jaw rearward.

·         Low-set ears.

·         A set of specific features of the eyes is presented.

·         Lack of tear duct.

 

 

 

 

 

 

 

 

 

 

 

 

Although it is difficult to determine the frequency of this syndrome in newborn infants, has been estimated at between 1 / 50,000 to 1 / 20,000 births, and has been observed in all ethnic groups, most of them in women than men in a ratio of two one.

Medical Complications

·         Seizures: can start early from 9-10 months.

·         Congenital heart diseases: coarctation of the aorta, atrial septal defect, ventricular septal defect.

·         Hypospadias: malformation in which the male urethral opening is not located at the tip of the penis but in its bottom. In 50% of patients.

·         Malformations in the kidneys: incomplete or faulty development or absence of a kidney (less than 10% of cases)

 

Causes

The Wolf-Hirschhorn syndrome is caused by partial deletion of the short arm of chromosome IV, in particular in the region WHSC1 and WHSC2.

About 87% of the cases represent a de novo deletion, while about 13% are inherited from a parent with a chromosomal translocation. The severity of symptoms and the expressed phenotype vary depending on the amount of genetic material has been removed. The critical region for determining the phenotype is in 4p16.3 and often can be detected by genetic and fluorescence in situ hybridization tests. It should always be offered genetic counseling to affected families with Wolf-Hirschhorn syndrome.

 

Cytogenetic diagnosis

The clinical diagnosis is not certain, but a suspicion that requires confirmation with the definite diagnosis obtained from cytogenetic analysis and / or molecular. By high resolution chromosome study (500-850 bands) the deletion was detected only in 70% of cases with clinical diagnosis. This is because the loss of the end of the short arm of chromosome 4 may be very small, and techniques need whose resolution is higher. At present, the most used is the fluorescence in situ hybridization (FISH), with which the deletion is detected in up to 95% of patients with clinically suspected.

Treatment
So far there is no treatment for this disease. Treatment is directed to reduce medical complications that arise in each particular case. The prognosis is grave, about a third of patients die before two years of age, cardiological bronco pulmonary complications, and few cases have been described with 10-16 years than survival. Survivors have severe mental retardation and growth retardation prone to recurrent infections bronchopulmonary. It is associated with a deletion in the short arm of chromosome 4 (4p16.3). Most cases are 85-90% novo deletions.

Bibliography:

•  Alexandra M.D.; Isabella.; Maria Luisa M.F .; Maria D. S .; and Maria Luisa M.F .. (April 2010). Wolf-Hirschhorn syndrome. A S E R E M E C E M AC C, 20, 1-2.

•  Article: Wolf-Hirschhorn syndrome. May 28, 2011. Available at: "yasalud.com". Accessed: February 23, 2012.

•  Dr. Iacobini, Sandra.; Dra. Lotersztein, Vanessa and equipment. Medical News: "Rare diseases" or "orphan". Available in: "www.intramed.net". Cosnultado: February 23, 2012.

•  Aviña orge A. F .; Daniel A. Hernández A. Wolf-Hirschhorn Syndrome: distal microdeletion short arm of chromosome 4. 3 November 2007. Available at: "www.scielo.cl". Cosnultado: February 23, 2012.

WERNER SYNDROME

I share an important fact about why the name of Werner syndrome and clinical manifestations were analyzed spending time And the genes that are associated with Werner syndrome.

Werner Syndrome was first described by Dr. Otto Werner at the Kiel University in 1904 (Werner, 1904). In his thesis, Dr. Werner described scleroderma-like skin and cataracts in a sibship. Because this disorder shares some aspects of aging as described for two Japanese-American sisters, WS has been described as the "caricature of aging" (Epstein et al., 1966). 

Symptoms of some aging disorders, such as Hutchinson-Gilford progeria, may start to develop as early as infancy (Brown et al., 1985). In contrast, WS patients usually develop normally until they lack the pubertal growth spurt during adolescence, a symptom often recognized only retrospectively. Previous studies indicate that, although patients suffer a wide variety of age-related disorders, the chronology of symptoms appear to be similar between Caucasian and Japanese WS patients (Epstein et al., 1966; Goto et al., 1997). 

Individuals with the WRN null mutations prematurely develop an aged- appearance and age-related disorders including graying of the hair, hair loss, tight skin, cataracts, diabetes mellitus, hypogonadism, osteoporosis, atherosclerosis and cancers (Epstein et al., 1966; Martin et al., 1978; Tolesfbol and Cohen, 1984; Goto et al., 1997). The average age of clinical diagnosis of this syndrome is in the late thirties, and death usually occurs before the age of 55. The most common cause of death is cancer, followed by a vascular disease such as atherosclerosis (both myocardial and cerebrovascular). 


What genes are related to Werner syndrome?

Mutations in the WRN gene cause Werner syndrome. The WRN gene provides instructions for producing the Werner protein, which is thought to perform several tasks related to the maintenance and repair of DNA. This protein also assists in the process of copying (replicating) DNA in preparation for cell division. Mutations in the WRN gene often lead to the production of an abnormally short, nonfunctional Werner protein. Research suggests that this shortened protein is not transported to the cell's nucleus, where it normally interacts with DNA. Evidence also suggests that the altered protein is broken down more quickly in the cell than the normal Werner protein. Researchers do not fully understand how WRN mutations cause the signs and symptoms of Werner syndrome. Cells with an altered Werner protein may divide more slowly or stop dividing earlier than normal, causing growth problems. Also, the altered protein may allow DNA damage to accumulate, which could impair normal cell activities and cause the health problems associated with this condition.