Holoprosencephaly

What is Holoprosencephaly? ● Holoprosencephaly, according to the National Human Genome Institute (2009), is a common birth defect affecting the brain. ● The procensephalon, or the front of the brain, does not divide into the two lobes of the cerebral hemispheres. ● Babies born with the severe form of this condition suffer from extreme skull and facial distortions and often die before birth while babies born with the less severe form of this condition are born with an almost normal brain and mild deformities of the face.

Classifications of HP The National Institute of Neurological Disorders and Stroke (2007) has classified HP as follows: I. Alobar- the brain has no development. The condition is extremely severe. II.Semi-lobar- the two lobes of the brain are somewhat developed. The condition is moderate. III. Lobar- the two lobes of the brain seem to be almost completely developed. The condition is mild.

Severity of Facial Deformities ● Premaxillary agenesis, or a cleft lip, is the least severe. ● Cyclopia is the most severe. The baby is born with one eye in the middle of the face where the nose is meant to be. ● Ethmocephaly, the most uncommon deformity, is when a proboscis nose, such as that of a proboscis monkey, is in between a close set of eyes. ● Cebocephaly can be acknowledged if the child has a nose with one nostril placed underneath and between close and underdeveloped eyes.

Premaxillary Agenesis

Cyclopia

Commonality of HP ● The Carter Centers for Brain Research in Holoprosencephaly and Related Malformations states that HP “affects between 1 in 5,000-10,000 live births.” Unfortunately, many pregnancies end in miscarriages if the baby is affected with HP, so the likelihood of HP among all pregnancies may be 1 in 250. ● Studies also show that only 3% of babies with HP survive birth and the ones that do will most likely die within the first six months of life. However, the life expectancy of a baby born with HP largely depends on the severity of the defect and lifestyle. In the most severe cases, babies may live only a couple years. The CCBRHRM also claims that “Almost two-thirds of affected patients have alobar HP and approximately one quarter are diagnosed with semilobar HPE.” There is no evidence showing HP discriminates against race or gender.

Diagnosis ● According to Agarwal (2000), ultrasounds are “reliable in the prenatal diagnosis” of HP. The cosmetic deformities can be seen as early as the second trimester of the pregnancy through ultrasounds. ● Images of the skull are taken by coronal sonograms, which are images taken by sound to asses the brain, and mid-sagittal sonograms, which allow the facial features to be seen clearly when in the womb (Agarwal, 2000).

Diagnosis (Cont.) ● When the baby is born, it may be diagnosed with HP if he or she has an incredibly small head (microcephaly) and has facial deformities (Gilman, 2005). ● Magnetic resonance imaging (MRI) is a way to diagnose the less severe cases of HP using radiology (Gilman, 2005).

Transmission ● The transmission of Holoprosencephaly is not yet completely understood. Twenty to twenty- five percent of all patients have some sort of structural or numeral choromosomal abnormalities (Holoprosencephaly, 2006). Patients have an extra copy of chromosome thirteen (trisomy 13), an extra copy of chromosome fifteen (trisomy 15), and an extra copy of chromosome 18 (trisomy 18) (Holoprosencephaly, 2006).

Transmission (Cont.) ● “According to the National Institute of Neurological Disorders and Stroke, children of diabetic mothers appear to have an increased risk of HP (Holoprosencephaly, 2006).” ● Also, women who have had miscarriages in previous pregnancies or bleeding in the first trimester of pregnancy have an increased risk of having a child with HP (Holoprosencephaly, 2006).

Transimission (Cont.) ● Gilman (2005) stated that HP can “run in families as an autosomal recessive, dominant or X-linked recessive gene.” ● Research has shown that HP can be linked to 12 chromosomal regions on 11 chromosomes (Gliman, 2005).

Transmission (cont.) ● If a male with the genotype Hh (H being dominant for not having HP and h being recessive for having HP) mated with a female with genotype Hh, here are the possibilities of their offspring having HP. ● 25% will have HH (will not have recessive h chromosome), 50% will have Hh (may pass on recessive chromosome to offspring), and 25% will have both the recessive chromosomes of HP and will suffer from HP.

Signs & Symptoms ● Microcephaly- small head ● Hydorcephalus- excess liquid in the brain ● Epilepsy- random seizures ● Spasiticity- tightening and shortening of muscles ● Facial Deformities- cleft lip, close-set eyes, cebocephaly (small, flat nose below not fully developed eyes), one upper middle tooth, cyclopia (one eye in place of the nose), missing nose or proboscis nose, proboscis between two eyes.

Signs &Symptoms (Cont.) ● Sleep disorders- sleep apnea (person stops breathing for short periods of time during sleep) due to facial deformities ● Mental Retardation- levels of retardation vary with each patient. Some may require life-long care and others may be able to live on their own. ● Gastrointestinal issues- gastroesophageal reflux disease (stomach acids back up into esophagus) because of weak throat muscles ● (Holoprosencephaly, 2006)

Treatment ● There is no treatment for Holoprosencephaly. ● Most medications relieve symptoms of HP. ● Surgery can be performed for cosmetic reasons; for example: a cleft lip Before After