The Wolf-Hirschhorn syndrome it is a rare genetic pathology whose clinical characteristics are mainly due to the loss of genetic material. It is characterized by the presence of alterations related to facial malformations, seizures and a significant generalized delay in development..
It is associated with a number of important medical complications: neurological injuries, cardiac, musculoskeletal, immune, visual, auditory, genitourinary, etc..
Regarding the etiological origin of Wolf-Hirschhorn syndrome, it is associated with the presence of genetic abnormalities on chromosome 4. On the other hand, the diagnosis is usually confirmed during childhood, thanks to the recognition of physical and cognitive characteristics. However, genetic analysis is of vital importance.
Finally, the therapeutic intervention of this pathology is usually based on physical rehabilitation, speech therapy, the provision of antiepileptic drugs, nutritional adaptations or neuropsychological intervention, among other support measures..
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This disease was described simultaneously by researchers Ulrich Wolf and Kart Hirschhon, in parallel in 1965. In the first clinical reports, reference was made to a disorder characterized by the presence of microcephaly, with a cranial configuration similar to a greek helmet.
However, it was Zollino and his work group who described in 2001, in detail, all the clinical characteristics of Wolf-Hirshhorn syndrome..
To date, more than 90 different cases have been identified in the medical and experimental literature, generally associated with the female gender..
Furthermore, current definitions of this pathology cover both the identification of major or cardinal manifestations (atypical facies, growth retardation, delayed motor and cognitive development and epileptic disorders), as well as other medical manifestations (cardiac, sensory, genitourinary anomalies, etc. ).
Wolf syndrome is a pathology of genetic origin that is characterized by a mulsystemic involvement, defined by the presence of atypical facial characteristics, generalized growth retardation, intellectual disability and seizures..
However, the clinical course is widely heterogeneous among affected individuals, due to its genetic nature, the product of a deletion. By chromosomal deletion we understand the loss of one or more segments of a chromosome. Depending on the severity of this anomaly and the level of genetic involvement, differential characteristics may appear among those affected..
In this sense, the deficit of genetic material in this syndrome is associated with important medical complications. Thus, a large part of those affected die during the prenatal or neonatal phase, however, some cases of moderate severity exceed the first year of life.
In general, Wolf-Hirschhorn syndrome and its defining clinical features are considered rare medical conditions of genetic origin..
Despite its low prevalence, some statistical studies have managed to identify data associated with an incidence of 1 case per 50,000 births.
Other authors such as Blanco-Lago, Málaga, García-Peñas and García-Ron, point out that the Wolf-Hirschhorn syndrome can reach a prevalence close to 1 case per 20,000 births.
Regarding the sociodemographic factors associated with Wolf-Hirschhorn syndrome, a higher prevalence has been identified in females, specifically with a 2: 1 ratio compared to males..
Furthermore, it has not been possible to identify a differential frequency associated with specific geographic regions or specific ethnic and / or racial groups..
Finally, referring to hereditary factors, research has indicated that in more than 80% of those affected, this pathology is due to a random mutation. Cases of Wolf-Hirschhorn syndrome of hereditary genetic origin are rare.
The symptoms that can be observed in people suffering from Wolf-Hirschhorn syndrome can be highly variable, however, this syndrome is a pathology defined by several central medical conditions:
- Facial abnormalities.
- Widespread developmental delay.
- Convulsive episodes.
- Psychomotor and cognitive delay.
The cranio-facial characteristics are usually defined by a wide list of anomalies and alterations- Together, all of them have an atypical facial appearance, similar to the helms of Greek warriors..
Some of the most frequent clinical findings in this area are related to:
- Microcephaly: the cranial perimeter does not usually develop normally, so the total size of the head is usually smaller than expected for the chronological age of the affected person. Generally, various asymmetries can also be observed between the different structures that make up the craniofacial area..
- Nasal configuration: The nose is usually abnormally large, the upper part of which is flat, with a wide separation of the region between the eyebrows. In some cases, the nose takes an abnormal shape, commonly called a “parrot-beak” nose..
- Facial configuration: the jaw is usually poorly developed, with a small chin or chin being observed. In addition, the eyebrows often show an arched appearance. In addition, other pathological features such as vascularized spots, skin excretions, among others, usually appear..
- Atrial pinna implantation: the ears are usually located in a lower position than usual. In addition, it is possible to observe an underdevelopment of the ears, appearing smaller and more prominent than usual..
- Eye configuration: the eyes usually appear widely separated and with a significant symmetry, one of the eyeballs being smaller. In addition, we can identify strabismus, alterations in the structure and color of the iris, droopy eyelids or obstruction of the tear ducts.
- Oral disorders: in the case of the oral configuration, the most common is to identify an abnormally small labial filtrum, cleft lip, late dental hatching, cleft palate, among others.
In Wolf-Hirschhorn syndrome, it is possible to identify a generalized delay in growth and development, both in the prenatal and postnatal and infantile stages..
In this sense, children who suffer from this pathology tend to grow abnormally slow, so they usually have a lower weight and height than expected for their sex and chronological age..
These types of characteristics are not usually associated with difficulties in eating or deficits in caloric intake, however, both genetic alterations and the development of other types of pathologies, such as cardiac alterations, can contribute to the worsening of this medical condition.
In addition, generalized growth retardation is often related to various musculoskeletal abnormalities:
Seizures are one of the most frequent and serious symptoms in Wolf-Hirschhorn syndrome.
In this sense, seizures are defined as a pathological process resulting from an unusual neuronal activity that is altered causing motor agitation, muscle spasms, or periods of unusual behavior and sensations and can sometimes cause loss of consciousness..
In the case of Wolf-Hirschhorn syndrome, the most common seizures are tonic-clonic..
Thus, seizure episodes are characterized by the development of muscle tension, tending to generalized stiffness, especially in the legs and arms, followed by repetitive and uncontrolled muscle spasms. Visually, they can be seen as shaking of the body.
Furthermore, the severity of this event lies in its effect on brain tissue. Abnormal and / or pathological neuronal activity can affect a large part of the brain structure locally or generally, which is why they can have important neurological consequences and sequelae..
In the case of the cognitive sphere, more than 75% of those affected by Wolf-Hirschhorn syndrome have some type of intellectual disability.
Generally, the intellectual impairment is usually serious, they do not usually develop language skills so, in most cases, communication is limited to the emission of some sounds.
In addition, in the case of the acquisition of postural control, standing, gait, etc., all of these are significantly delayed, mainly due to musculoskeletal abnormalities.
In most cases, the signs and symptoms tend to develop progressively, so several stages can be distinguished in the development of this pathology:
In the earliest stages, the most characteristic symptoms are related to low weight and craniofacial abnormalities. In many cases, approximately 35%, affected individuals die due to the parallel presence of congenital heart defects.
In addition to the delay in physical development, psychomotor deficits are especially evident, in addition to musculoskeletal malformations. Along with these medical findings, seizures recur. Generally, few affected are able to walk or master the language.
In this phase, the characteristics related to the development and intellectual functioning are the most significant, however, the typical facial features become apparent monstrosities..
As we pointed out in the initial description of Wolf-Hirschhorn syndrome syndrome, this disorder is due to a genetic deletion located on chromosome 4.
Although the volume of loss of genetic material can vary considerably among affected individuals, the more severe and significant this is, the more serious the symptoms associated with this disease will present..
Although not all the genes involved are known exactly, different studies have linked the absence of the WHSC1, LEMT1 and MSX1 genes with the clinical course of Wolf-Hirschhorn syndrome.
A diagnosis of Wolf-Hirschhorn syndrome can be made before birth.
Pregnancy control ultrasounds allow the identification of intrauterine growth disorders and other types of physical malformations.
However, it is essential to carry out a genetic study to confirm your condition, either through pre or post-natal cell analysis..
There is currently no cure for Wolf-Hirschhorn syndrome, nor is there a standard therapeutic approach, so treatment is specifically designed based on individual characteristics and the clinical course of the disease.
Thus, normally medical intervention focuses on the treatment of seizures through the administration of antiepileptic drugs, nutritional supplements, surgical correction of physical malformations, cognitive rehabilitation and special education..
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