Holoprosencephaly: Causes, Symptoms & Treatment

Holoprosencephaly is a malformation of the human brain that occurs with relatively high frequency. A large proportion of affected embryos die in the womb. Therefore, only a few patients with holoprosencephaly are born alive. Holoprosencephaly forms prenatally and primarily affects the face and the frontal area of the brain.

What is holoprosencephaly?

Holoprosencephaly is relatively common, with a prevalence of between one and four cases per 1000 pregnancies. However, most affected infants die while still in utero, so the condition actually affects between 5000 and 20 000 patients born alive. Holoprosencephaly occurs more often in females than in males. About half of those with the disease have aberrations in chromosomes. Therefore, it is necessary to perform chromosome analysis in affected patients. Holoprosencephaly is particularly common in babies born to relatively young women. Holoprosencephaly forms between the third and sixth week of the embryo‘s life. The cause is that the anterior area of the brain does not divide completely. The malformation results from impairments at the midlines of the skull. The forebrain, which consists of the diencephalon and the endbrain, does not differentiate completely.

Causes

The exact processes and causes of the pathogenesis of holoprosencephaly are not known. In the majority of cases, holoprosencephaly presents sporadically. However, genetic factors probably also exist, such as an undersupply of the substance cholesterol. This favors the developmental disorder of holoprosencephaly. There are also various favorable factors for the development of holoprosencephaly in the mother. For example, diabetes mellitus, toxoplasmosis and viral infections of the embryo have a favorable effect on the development of the disease. Various external factors such as retinoic acid or hypocholesterolemia may also support the formation of holoprosencephaly. In addition, there are numerous genetic diseases that are associated with a higher than average incidence of holoprosencephaly. These include chromosomal anomalies such as trisomy 13, Joubert syndrome, trisomy 18, and the so-called 18p syndrome. Basically, an autosomal recessive or autosomal dominant mode of inheritance of holoprosencephaly is suspected.

Symptoms, complaints, and signs

Holoprosencephaly is associated with a variety of signs; however, the range of possible symptoms in different individuals is extraordinarily wide. For example, some patients with holoprosencephaly suffer from a cleft lip and palate, close spacing of the eyes, or a single incisor located in the middle. Other possible conditions include cyclopia, arrhinencephaly, and agenesis. Sometimes a so-called corpus callosum agenesia occurs. Alobaric, lobar, or semilobar holoprosencephaly are seen in the brain.

Diagnosis and course of the disease

Diagnosis of holoprosencephaly is possible in modern times using prenatal examination methods. Primarily, fine ultrasound techniques are used. In this way, holoprosencephaly can be diagnosed at relatively early stages in embryos in the womb. Semilobar and alobar holoprosencephaly are usually detected comparatively quickly. In contrast, the diagnosis of lobar holoprosencephaly is often much more difficult. As soon as the presence of holoprosencephaly in the embryo is confirmed, the parents are given the option of terminating the pregnancy for medical reasons. If they decide to keep the child, appropriate measures must be taken. These relate first of all to the selection of the maternity hospital so that the newborn is optimally cared for. The diagnosis of holoprosencephaly is also performed again or for the first time after birth. In this process, the physician usually uses various imaging techniques. These include, for example, an MRI scan, sonography, and computed tomography.

Complications

In most cases, holoprosencephaly causes the child to die while still in the womb due to the various malformations in the brain.In many cases, this results in psychological complaints and depression in the child’s parents, which must be treated by a psychologist. It can often take years before the psychological symptoms improve. If the child does not die before birth, various malformations and deformities occur. In most cases there is cyclopia or cleft palate. This has a very negative influence on the patient’s everyday life. Often, the affected person also has only one incisor tooth, which complicates the fatal food gain as well. There can also be severe complications during the birth of the child. In many cases, even after the birth, the parents suffer from psychological discomfort due to the child’s deformities. Unfortunately, it is not possible to treat holoprosencephaly causally or symptomatically, so the child dies in the first months. However, in rare cases, the child may survive the first year of life and has increased chances of complete survival thereafter.

When should you see a doctor?

Holoprosencephaly must definitely be examined and treated by a doctor. There is no self-healing in this disease, and in many cases, death of the affected person. Often the children die in the womb, so that no further treatment is possible. A visit to the doctor can help diagnose holoprosencephaly, as the symptoms can be detected during an ultrasound examination. The mother does not experience any other symptoms. However, regular examinations can detect holoprosencephaly early. In case of stillbirth or death of the child shortly after birth, the affected parents should consult a psychologist to avoid psychological distress. If the child is born alive, the parents need strong support from various doctors to keep the child alive. The child is usually dependent on a stay in the hospital.

Treatment and therapy

Currently, holoprosencephaly has no causative treatment. Therefore, patients usually receive symptomatic treatment that is tailored to the individual case. In principle, most babies with holoprosencephaly die in the womb. The prognosis of patients born alive also tends to be negative. Severe manifestations of holoprosencephaly lead to death in most cases within the first months of life. The form of holoprosencephaly also affects the prognosis of the disease. Thus, the disease is less favorable in the alobaric type than in the lobar or semilobaric type. Patients who survive their first year of life often have a more favorable course of holoprosencephaly. In numerous cases, these individuals reach adulthood. However, these individuals also suffer from physical and cognitive disorders as well as neurological impairments. These manifest themselves, for example, in epileptic seizures. Sometimes the affected children are unable to develop spoken language. Sleep disorders are also comparatively common in those affected by holoprosencephaly.

Outlook and prognosis

The prognosis of holoprosencephaly is extremely unfavorable. A majority of affected patients die in the abdomen during the developmental phase. The disease develops in the womb during the first weeks of the growing embryo and cannot be treated. A diagnosis is made during the control visits within a pregnancy while still in the womb, yet there is no possibility of initiating treatment or correcting the genetic defect. If birth occurs, many newborns die immediately after delivery. Survivors cannot be adequately treated. They are born with sometimes severe malformations of the brain that cannot be changed. Treatment is based on the symptoms present and is used to alleviate symptoms. The lifespan of a newborn with holoprosencephaly is significantly reduced. In addition, the patient will be dependent on outside help for the rest of his or her life. Various dysfunctions occur and severe mental retardation is present. In addition to the poor prognosis for the affected person, there are sequelae or illnesses of the relatives. The mental stress can lead to a psychological disorder in the parents.In addition to anxiety disorder, trauma, or depression, long-term impairment of well-being and loss of enjoyment of life are possible due to the unfulfilled desire to have a child or the occurrence of a stillbirth.

Prevention

The causes of holoprosencephaly are not fully understood and, in the vast majority of cases, elude control. This is because the disease is primarily caused by genetic and external factors. Only certain identified risk factors are partially within the control of the expectant mother. These include diabetes mellitus, for example. In addition, studies show that holoprosencephaly particularly affects very young pregnant women. Through prenatal examinations, holoprosencephaly can be detected early in the unborn child.

Follow-up

Unfortunately, a large proportion of children affected by holoprosencephaly already die while still in the womb or immediately after birth. In these cases, aftercare is limited to psychological support for the relatives. This should be provided primarily by the child’s own family and close friends, and can be supplemented by psychotherapeutic therapy if necessary to reduce the risk of depression or other psychological complaints. Provided the child was born alive, he or she must receive intensive medical care to keep him or her alive. In most cases, this is done during the first months of life as part of a long hospital stay. Parents gradually become involved in the care and can later also advocate for receiving intensive medical care as part of their home care. If the child survives the critical first year of life, it is a positive outcome and there is a high probability of reaching adulthood. However, due to the many physical and cognitive disorders as well as neurological impairments, they will be dependent on outside help throughout their lives. Relatives should ensure that regular check-ups are observed and that any epileptic seizures and other symptoms and complaints that occur are treated appropriately by the physician.

What you can do yourself

It is not possible to treat holoprosencephaly by self-help means. In this case, many of the affected children die either in the womb or immediately after birth. In case of early death, the parents need psychological support. This should be provided primarily by close friends or by the parents’ own family. But also the contact to a psychologist can be a help for affected parents. Through that help, psychological complaints or even depression can be avoided and reduced. If the child survives the first years of life, it can in many cases also reach adulthood. However, the patients are dependent on help in their everyday life, since they cannot carry out many things of the everyday life alone. Ideally, this help is provided by the patient’s own parents, relatives or friends. On a psychological level, too, contact with other people always has a positive effect on the course of the disease. Cognitive disorders can be alleviated by various exercises. In case of an epileptic seizure, however, immediate medical treatment is necessary. Often, contact with other parents whose child has holoprosencephaly can also have a positive effect on the disease and the quality of life, as it leads to an exchange of information.