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Children severely affected by holoprosencephaly typically do not live beyond early infancy, whereas mildly affected children survive past 12 months.
Holoprosencephaly (HPE) is a developmental abnormality in which the brain doesn’t separate into two different hemispheres. HPE malformation is mostly seen in the forebrain.
During the 18th and 28th days after conception, the embryonic forebrain divides into two cerebral hemispheres. HPE is the condition in which the midline division of the embryonic forebrain is imperfect or missing, and it is retained as one whole brain.
The life expectancy of HPE depends on the severity of the defect.
- A fetus with a severe type of HPE is usually born as a stillbirth or dies immediately after birth or during the first six months of life.
- However, a considerable number of slightly affected children and some severely affected children survive past 12 months.
HPE is a rare disease and is estimated to be 1 in 250 during the early embryonic stage and 1 in 16,000 live births.
What are the causes of holoprosencephaly?
Holoprosencephaly (HPE) is caused by the following:
- Mutations in at least 14 distinct genes and chromosomal abnormalities
- Teratogens (harmful substances that if ingested by the mother during pregnancy may cause birth defects)
- HPE may be a characteristic of several rare genetic disorders such as Smith-Lemli-Opitz syndrome
- Gestational diabetes in the mother during pregnancy is a minor risk factor
Although there are various known risk factors, the exact cause of HPE may be unknown in several cases. The life expectancy and treatment depend on the symptoms and severity of the defect.
4 subtypes of holoprosencephaly
Holoprosencephaly (HPE) is divided into four types:
- Alobar HPE:
- One of the most severe forms where the brain is not divided into right and left hemispheres and remains as one.
- Certain parts in the brain do not develop during embryonic growth such as the corpus callosum (a band that connects two halves of the brain), rhinencephalon, and a single ventricle with fused thalami (midbrain). Facial features are always affected.
- Cyclopia is seen in this type of HPE, which is a congenital abnormality in which an infant has a single eye placed in the center of the face, occupying the place of the roof of the nose.
- Semi-lobar HPE:
- Although the cerebral hemispheres are united anteriorly, they are separated posteriorly.
- The corpus callosum has agenesis (failure of development during the embryonic stage) or hypoplasia (poorly developed), and the olfactory bulbs and tracts are frequently missing. Facial characteristics are frequently harmed.
- Patients with semi-lobar HPE may have the following:
- Hypotelorism (an abnormal decrease in the distance between two organs) of the eyes
- Microphthalmia (one or both eyes do not develop completely and remain small)
- Anophthalmia (absence of one or both the eyes)
- Flattened bridge and tip of the nose
- One nostril
- Medial cleft lip
- Bilateral cleft lip
- Cleft palate
- Lobar HPE:
- The cerebral hemispheres are completely divided, but the corpus callosum and olfactory lobes may be underdeveloped.
- Facial characteristics may be unaffected or impacted only to a lesser extent; they include
- Bilateral cleft lip
- Closely spaced eyes
- Depressed nose
- Middle interhemispheric:
- The least severe form occurs when the posterior frontal and parietal lobes are not completely divided.
- Patients may present with closely spaced eyes, a depressed and narrow nose, or an almost normal-looking face.
What are the signs and symptoms associated with holoprosencephaly?
The signs and symptoms associated with holoprosencephaly include:
- Seizures/epilepsy
- Hydrocephalus (big head)
- Neural tube defects
- Pituitary dysfunction
- Short stature
- Development delays include intellectual disability depending on the extent of brain defect
- Motor problems
- Hypotonia
- Dystonia
- Spasticity
- Difficulty swallowing and dysphagia (pain with swallowing)
- Pulmonary problems, especially during aspiration
- Gastrointestinal problems
- Gastroesophageal reflux
- Slow gastric emptying
- Constipation
- Hypothalamic problems
- Abnormal sleep-wake cycles
- Temperature dysregulation
- Diabetes insipidus
- Hypothyroidism
- Hypoadrenocorticism
- Growth hormone deficiency