He Wolf-Hirschhorn syndrome Is a rare genetic pathology whose clinical features are primarily due to the loss of genetic material (Wolf-Hirschhorn Syndrome Association, 2012).
At the clinical level, this pathology is characterized by the presence of alterations related to facial malformations, convulsive episodes and an important generalized developmental delay (Aviña and Hernández, 2008).
Thus, at a specific level, it is associated with a number of important medical complications: neurological lesions, cardiac, musculo-skeletal, immune, visual, auditory, genitourinary, etc. (Blanco-Lago, Málaga, García-Peñas, García-Rom, 2013).
As for the etiological origin of Wolf-Hirschhorn syndrome, this is associated with the presence of genetic abnormalities on chromosome 4 (Coppola, Chinthapalli, Hammond, Sander, Sisodiya, 2013).
On the other hand, the diagnosis of Wolf-Hirschhorn syndrome is usually confirmed during the infantile stage, thanks to the recognition of the physical and cognitive characteristics. However, genetic analysis is of vital importance (Spanish Association of Wolf-Hirschhorn Syndrome, 2012).
Finally, the therapeutic intervention of this pathology is usually based on physical rehabilitation, speech therapy, antiepileptic drug delivery, food adaptations or neuropsychological intervention, among other support measures (Medina, Rojas, Guevara, Cañizales and Jaimes, 2008 ).
Characteristics of Wolf-Hirschhorn syndrome
Wolf syndrome is a pathology of genetic origin characterized by a multisystemic involvement, defined by the presence of atypical facial features, generalized growth retardation, intellectual disability and convulsive episodes (Genetics Home Reference, 2016).
However, the clinical course is widely heterogeneous among the affected individuals, due to the genetic character of this, product of a deletion (National Organization for Rare Disroders, 2016).
Thus, we mean by chromosomal deletion the loss of one or several segments of a chromosome (Chromosomal Mutations, 2016). Depending on the severity of this anomaly and the level of genetic involvement, differential characteristics may occur among those affected (National Organization for Rare Disroders, 2016).
In this sense, the genetic material deficit in Wolf syndrome is associated with important medical complications. Thus, a good part of those affected die during the prenatal or neonatal phase, however, some cases of moderate severity exceed the first year of life (WolfHirschhorn, 2013).
This disease was described simultaneously by researchers Ulrich Wolf and Kart Hirschhon, in parallel in 1965 (Aviña and Hernández, 2008).
In the first clinical reports, reference was made to a disorder characterized by the presence of Microcephaly , With a skull configuration similar to a Greek helmet (Aviña and Hernández, 2008).
However, it was Zollino and his work group who described in detail all the clinical features of Wolf-Hirshhorn syndrome in 2001 (Aviña and Hernández, 2008).
To date, more than 90 different cases have been identified in the medical and experimental literature, generally associated with the female gender (Blanco-Lago, Málaga, García-Peñas, García-Rom, 2013).
In addition, current definitions of this pathology encompass both the identification of major or cardinal manifestations (atypical facies, growth retardation, delayed motor and cognitive development and epileptic alterations), and other medical manifestations (cardiac, sensory, genitourinary abnormalities, etc.). ) (Spanish Association of Wolf-Hirschhorn Syndrome, 2016).
Is it a frequent pathology?
In general, Wolf-Hirschhorn syndrome and its defining clinical features are considered to be rare medical conditions of genetic origin (Spanish Association of Wolf-Hirschhorn Syndrome, 2012).
However, despite its low prevalence, some statistical studies have been able to identify data associated with an incidence of 1 case per 50,000 births (Aviña and Hernández, 2008).
However, other authors such as Blanco-Lago, Málaga, García-Peñas and García-Ron (2013), indicate that Wolf-Hirschhorn syndrome can reach a prevalence of close to 1 case per 20,000 births.
On the other hand, in relation to the sociodemographic factors associated with Wolf-Hirschhorn syndrome, a higher prevalence has been identified in females, specifically with a ratio of 2: 1 to males (Medina et al., 2008) .
In addition, it has not been possible to identify a differential frequency associated with specific geographic regions or specific ethnic and / or racial groups (Medina et al., 2008).
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 hereditary Wolf-Hirschhorn syndrome are rare (Medina et al., 2008).
Signs and symptoms
As we have pointed out previously, the symptoms that can be observed in people suffering from Wolf-Hirschhorn syndrome can be very variable, however, this syndrome is a pathology defined by several central medical conditions (Spanish Association of Wolf-Hirschhorn Syndrome , 2016).
- Facial anomalies.
- Generalized delay of development.
- Convulsive episodes.
- Psychomotor and cognitive delay.
Facial anomalies
The cranio-facial features are usually defined by an extensive list of abnormalities and alterations. Together, they all have an atypical facial appearance, similar to the helmets of the Greek warriors (Wieckzorek, 2013).
Some of the most frequent clinical findings in this area are related to: (Spanish Association of Wolf-Hirschhorn Syndrome, 2016, National Organizatio for Rare Disorders, 2016, Genetics Home Reference, 2016):
- Microcephaly : The cranial perimeter usually does not develop normally, so the total head size is usually lower than expected for the chronological age of the affected person. Generally, different asymmetries between the different structures that make up the craniofacial area can also be observed.
- Nasal configuration : The nose usually has an abnormally large size, the upper part of which develops flat, with a wide separation of the region between the eyebrows. In some cases, the nose takes on an abnormal shape, commonly referred to as"parrot beak"nose.
- Facial configuration : The mandible usually presents little developed, being able to be observed a small chin or chin. In addition, the eyebrows often show an arched appearance. In addition, other pathological features usually appear as vascularized spots, skin excretions, among others.
- Headset deployment : The ears are usually in a lower position than usual. In addition, it is possible to observe an underdevelopment of the ears, looking smaller and more prominent than usual.
- Eye configuration : The eyes usually appear widely separated and with a significant symmetry, being smaller one of the eyeballs. In addition, we can identify strabismus, alterations in the structure and color of the iris, fallen eyelids or obstruction of the lacrimal ducts.
- Mouth disorders : In the case of oral configuration, the most common is to identify an abnormally small lip phylltrum, cleft lip, late dental hatching, cleft palate, among others.
Generalized delay of development
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 (Aviña and Hernández, 2008).
In this sense, children who suffer from this pathology have to grow abnormally slow, so they are usually shorter in weight and height than expected for their gender and chronological age (Spanish Association of Wolf-Hirschhorn Syndrome, 2016 ).
These types of characteristics are not usually associated with feeding difficulties or caloric deficits, however, both genetic alterations and the development of other types of pathologies, such as cardiac alterations, may contribute to the worsening of this medical condition (Asociación Española Of Wolf-Hirschhorn Syndrome, 2016).
In addition, generalized growth retardation is often related to various musculoskeletal abnormalities:
- Muscular underdevelopment : The muscular structure does not usually develop completely, due to this is very frequent to observe an abnormally reduced muscle tone.
- Scoliosis and kyphosis : The bone structure of the spine may be defectively formed with a deviated position or with an abnormal curvature.
- Clinodactyly : The bone structure of the fingers also tends to develop abnormally, thus, it is possible to observe deviations in the fingers. In addition,
Alterations in the configuration of the fingerprints. - Abnormally Thin Extremities : Low weight is especially observable in the arms and legs.
Convulsive episodes
The convulsive crisis Are one of the most frequent and severe symptoms in Wolf-Hirschhorn syndrome (Spanish Association of Wolf-Hirschhorn Syndrome, 2016).
In this sense, seizures are defined as a pathological process resulting from an unusual neuronal activity that is altered causing motor agitation, muscular spasms, or periods of unusual behavior and sensations and can sometimes lead to loss of consciousness (Mayo Clinic .
In the case of syndrome of Wolf-Hirschhorn syndrome, the most common crises are tonic-clonic (Spanish Association of Syndrome Wolf-Hirschhorn, 2016).
Thus, convulsive episodes are characterized by the development of muscular tension, tending to generalized stiffness, especially in legs and arms, followed by repetitive and uncontrolled muscle spasms. At the visual level, they can be seen as shaking the body (National Institute of Neurogical Disorders and Stroke, 2015).
In addition, 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 generically, which can have important consequences and neurological sequelae (National Institute of Neurological Disorders and Stroke, 2016).
Psychomotor and cognitive delay
In the case of the cognitive sphere, more than 75% of those affected by Wolf-Hirschhorn syndrome present some type of Intellectual disability (Medina, Rojas, Guevara, Cañizales and Jaimes, 2008).
Usually, intellectual affection is usually severe, they do not usually develop their language skills, which means that, in most cases, communication is limited to the emission of some sounds (Medina, Rojas, Guevara, Cañizales and Jaimes, 2008).
In addition, in the case of acquisition of postural control, standing, walking, etc., all these are significantly delayed, mainly due to musculoskeletal abnormalities.
Clinical course
In most cases, signs and symptoms usually develop progressively, so that several stages can be distinguished in the development of this pathology (Wieczorek, 2003):
- First year of life : 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.
- Children's stage : In addition to delayed physical development, psychomotor deficits become especially evident, in addition to musculoskeletal malformations. Along with these medical findings, convulsions recur. Generally, few affected are able to get to walk or to master the language.
- Late childhood and adolescence : In this phase, the characteristics related to development and intellectual functioning are the most significant, however, typical facial features become obvious menses.
Causes
As noted in the initial description of Wolf-Hirschhorn syndrome, this disorder is due to a genetic deletion located on chromosome 4 (Genectis Home Reference, 2016).
Although the volume of loss of genetic material may vary considerably among affected individuals, the more severe and significant the genetic material is, the greater the severity will be the symptoms associated with this disease (Genectis Home Reference, 2016).
Although not all the genes involved are known accurately, different studies have related the absence of the WHSC1, LEMT1 and MSX1 genes, with the clinical course of Wolf-Hirschhorn syndrome (Genectis Home Reference, 2016).
Diagnosis
It is possible to diagnose Wolf-Hirschhorn syndrome before birth (National Organization for Rare Disorders, 2016).
The Ultrasound Of gestation control allow the identification of alterations in intrauterine growth and other physical malformations (National Organization for Rare Disorders, 2016).
However, it is critical to perform a genetic study to confirm your condition, either through pre or post natal cell analysis (National Organization for Rare Disorders, 2016).
Treatment
There is currently no cure for Wolf-Hirschhorn syndrome, nor a standard therapeutic approach, so the treatment is specifically designed based on the individual characteristics and clinical course of the pathology (WolfHirschhorn, 2013).
Thus, the medical intervention usually focuses on the treatment of seizures through the administration of antiepileptic drugs, the nutritional supplement, the surgical correction of physical malformations, the Cognitive rehabilitation And special education (WolfHirschhorn, 2013).
References
- AESWH. (2016). What is Wolf-Hirschhorn Syndrome? Retrieved from The Spanish Wolf-Hirschhorn Syndrome Association.
- . Wolf-Hirschhorn syndrome: Distal microdeletion of the short arm of chromosome 4. Rev Chil Pediatr, 50-53.
- Blanco-Lago, R., Málaga, I., García-Peñas, J.-J., & García-Ron, A. (2013). Wolf-Hirschhorn syndrome. Series of 27 patients: epidemiological and clinical characteristics. Current situation of patients and their caregivers' opinion regarding the diagnostic process. Rev Neurol, 49-56.
- Coppola, A., Chinthapalli, K., Hammond, P., Sander, J., & Sisodiya, S. (2012). Pediatric diagnosis not made until adulthood: A case Wolf-Hirschhorn syndrome. Gene, 532-535.
- Wolf-Hirschhorn syndrome. (2012). Spanish Association of Wolf-Hirschhorn Syndrome.
- Molina, R., Rojas, M., Guevara, R., Cañizales, E., & Jaimes, V. (2008). WOLF-HIRSCHHORN SYNDROME: REPORTING A CLINICAL CASE AND LITERATURE REVIEW. VENEZUELAN ARCHIVES OF CHURCH AND PEDIATRICS, 91-95.
- NIH. (2016). Wolf-Hirschhorn syndrome. Retrieved from the Genetics Home Reference.
- Mayo Clinic. (2015). Epilepsy. Obtained from Mayo Clinic.
- NIH. (2015). Epilepsy - overview. Obtained from MedlinePlus.
- NIH. (2016). The Epilepsies and Seizures: Hope Through Research. Retrieved from the National Institute of Neurological Disorders and Stroke.
- NORD. (2016). Wolf Hirschhorn Syndrome. Retrieved from the National Organization for Rare Disorders.
- Wieczorek, D. (2003). Wolf-Hirschhorn syndrome. Retrieved from Orphanet encyclopedia.
- Wolf-Hirschhorn Syndrome. (2013). Obtained from WolfHirschhorn.