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Nonsyndromic Holoprosencephaly

Last updated Dec. 11, 2018

Approved by: Maulik P. Purohit MD, MPH

Nonsyndromic Holoprosencephaly (HPE) is a rare developmental abnormality affecting the head and face.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Isolated Holoprosencephaly
  • Non-Syndromic, Non-Chromosomal Holoprosencephaly
  • Non-Syndromic, Non-Chromosomal HPE

What is Nonsyndromic Holoprosencephaly? (Definition/Background Information)

  • Nonsyndromic Holoprosencephaly (HPE) is a rare developmental abnormality affecting the head and face
  • Normally, the brain divides into right and left halves or hemispheres.  In Holoprosencephaly, the brain does not divide into two hemispheres, or only does so partially
  • Some genetic syndromes, such as Patau syndrome (trisomy 13), are known to cause Holoprosencephaly.  In contrast, “Nonsyndromic” Holoprosencephaly pertains only to cases of Holoprosencephaly that do not form a part of a genetic syndrome
  • However, the cause of Nonsyndromic HPE are genetic mutations, which may be inherited in an autosomal dominant manner in some cases
  • The brain structure condition does not worsen over time, as the baby grows

4 different types of Nonsyndromic Holoprosencephaly exist, based on the severity of the developmental abnormality. The different types, arranged from most severe to least severe, include:

  • Alobar
  • Semi-lobar
  • Lobar
  • Middle interhemispheric variant (MIHV)

Who gets Nonsyndromic Holoprosencephaly? (Age and Sex Distribution)

  • Nonsyndromic Holoprosencephaly approximately affects, 1 in 20,000 to 1 in 40,000 newborns
  • Both, male and female sexes are equally affected
  • Some experts believe that race or ethnicity may have a bearing on the incidence of the disorder. However, there are no clear statistics to establish the same

What are the Risk Factors for Nonsyndromic Holoprosencephaly? (Predisposing Factors)

Potential risk factors associated with Nonsyndromic Holoprosencephaly include:

  • The presence of any family member, sibling, or relative, with this condition
  • Pregnant women suffering from diabetes
  • Use of aspirin, before or during pregnancy
  • Pregnancies, using assisted reproductive technologies
  • Early menarche in women
  • Maternal age above 35, or below 25 years
  • Over 50% of the children with Nonsyndromic Holoprosencephaly have some form of genetic defects or chromosomal abnormalities
  • Exposure to a wide variety of environmental and chemical agents that are responsible for an assortment of developmental growth defects, such as:
    • Certain medications and drugs
    • Ionizing radiation
    • Infectious diseases
    • Imbalances during metabolism
    • Environmental chemicals and compounds

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Nonsyndromic Holoprosencephaly? (Etiology)

  • Nonsyndromic Holoprosencephaly can be caused by genetic mutations, in one or many genes, involved in brain and face development. Mutations in at least 11 different genes are known to cause Nonsyndromic HPE
  • The disorder may be inherited in an autosomal dominant pattern, which means that either parent can pass on the disease to their children. The severity of the disease varies, even within families
  • Other unknown genetic or environmental factors may play a role, in determining the severity of the disease

What are the Signs and Symptoms of Nonsyndromic Holoprosencephaly?

The signs and symptoms of Nonsyndromic Holoprosencephaly may include:

  • In the most severe forms of Nonsyndromic Holoprosencephaly (alobar type), the brain hemispheres and eyes do not divide, leaving one central eye (cyclopia). A tubular opening above the eye, called a proboscis, is also present
  • In less severe forms, the eyes separate, but may slant upwards at the corners
  • The ears may be enlarged
  • Openings along the roof of the mouth (cleft palate) or the upper lip (cleft lip) are common
  • The nose may be shortened and upturned, and the nasal bridge is often flattened. The space between the nose and mouth (called philtrum) can be broad. The sense of smell may be partially or completely absent
  • Some individuals have only a single front tooth, instead of the usual two; which is known as single maxillary incisor
  • Many affected individuals have an unusually small head (microcephaly). However, in some cases, fluid accumulation in the brain, known as hydrocephalus, can cause an unusually large head size (macrocephalus). Varying degrees of intellectual impairment may be present
  • Pituitary gland dysfunction is frequent, commonly resulting in diabetes insipidus. This causes problems in maintaining fluid balance
  • There may be abnormalities in regulating the body temperature, heart rate, normal feeding, and breathing
  • Seizures are seen in some affected individuals
  • Some individuals may only have very few outward abnormalities. In such cases, the disorder may be detected only after careful imaging studies of the brain are performed

How is Nonsyndromic Holoprosencephaly Diagnosed?

A diagnosis of Nonsyndromic Holoprosencephaly may involve:

  • Physical examination of the newborn child
  • Evaluation of the family medical history
  • Ultrasound studies conducted prenatally
  • Genetic testing and analysis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Nonsyndromic Holoprosencephaly?

The possible complications from Nonsyndromic Holoprosencephaly include:

  • Spontaneous abortions
  • Elective termination of the pregnancy, if the condition is severe

How is Nonsyndromic Holoprosencephaly Treated?

Nonsyndromic Holoprosencephaly disorders have no known cures. An individualized treatment (a case-by-case approach) is planned and provided, based on the specific conditions or complications that develop.

  • In those who survive the first few years, some of the physical defects may be corrected and surgical procedures may be performed
  • But, for improving motor skills and mental disabilities, special therapeutic treatment (by speech, physical, and occupational therapists) and supportive care is necessary

How can Nonsyndromic Holoprosencephaly be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Nonsyndromic Holoprosencephaly genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Some of the risk factors that potentially lead to this condition should be recognized and avoided
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Nonsyndromic Holoprosencephaly? (Outcomes/Resolutions)

  • Severe cases of Nonsyndromic Holoprosencephaly, frequently results in the death of the fetus prior to birth
  • Life expectancy in individuals, who survive to birth, varies greatly and depends on the severity of the symptoms

Additional and Relevant Useful Information for Nonsyndromic Holoprosencephaly:

Holoprosencephaly disorder is known to occur in other animal species too.

What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: March 4, 2014
Last updated: Dec. 11, 2018