Holoprosencephaly

The holoprosencephaly (HPE ) is a prenatal ( before birth ) malformation resulting in the area of the forebrain and face.

Frequency

In about one to four out of 1,000 pregnancies holoprosencephaly occurs in children and thus represents the most common congenital brain malformation dar. However, since most babies are not viable, is born due to the high intrauterine lethality only one 2500-16000 children with holoprosencephaly alive. Girls are affected more often than boys ( Gynäkotropie ) and the malformation is above average often found in children of very young mothers.

Formation

The malformation occurs in approximately third to sixth week of embryonic development by incomplete division of the forebrain as a result of a disturbance in the area of ​​the center line development field of the head: It is not the complete division or differentiation of the forebrain ( forebrain ), which consists of the telencephalon ( Cerebrum ) and the diencephalon ( diencephalon ) composed.

Causes

The precise causes (etiology ) of holoprosencephaly is still not much known. In most cases, the occurrence of randomly ( sporadically), but apparently can ( with ) cause the developmental disorder, a genetic deficiency of cholesterol. Risk factors include diabetes mellitus pregnant women, viral disease of the fetus, toxoplasmosis, various teratogens and environmental factors also apply, such as Hyperglycemia, hypocholesterolemia, retinoic acid and ethanol, which can influence.

Statistically found in about 50 out of 100 children clear differences at the chromosomal level (eg, trisomies ) and a further 20 changes can be detected by specific molecular genetic techniques. The cause of holoprosencephaly in the remaining 30 children can not currently be linked to genetic reasons.

More than 25 diseases with a genetic background associated with an increased likelihood of a holoprosencephaly. This includes features such as chromosomal triploidy, trisomy 13 ( Patau syndrome), trisomy 18 ( Edwards syndrome), 18p - syndrome and Joubert syndrome. In studies of genetic factors previously holoprosencephaly five loci (HPE ) were found: localization to 21q22.3 ( HPE1 ), 2p21 ( HPE2; SIX3 gene Wallis, 1999), 7q36 ( HPE3; sonic hedgehog gene), 18p ( HPE4 ) and 13q32 ( HPE5 ) / cf Roessler, Erich / Philadelphia. The mode of inheritance appears to be autosomal dominant or autosomal recessive.

Features and diagnosis

The expression has a wide range of: clinically silent mutation sponsorship, cleft lip and palate (also median pseudo columns), light shapes (eg with only one central incisor, hypotelorism / closely-spaced eyes) occur as well as Arrhinencephalie, Corpus - callosum agenesis, agenesis of the pituitary gland and disorders with cyclopia. About nine out of ten children have other malformations.

Anatomically be distinguished:

• Alobäre holoprosencephaly ( no separation, no interhemispheric fissure, a ventricle of the brain )
• Semilobar holoprosencephaly ( partial separation, posterior interhemispheric fissure with rudimentary hemispheres, one brain ventricles )
• Lobar holoprosencephaly (separation is mostly done, complete interhemispheric fissure, two lateral ventricle with rudimentary connection)

The diagnosis can be prenatally in the context of prenatal diagnosis by ultrasound examinations especially fine in the second trimester, some even earlier found. While the finding of alobären and semilobären form is often quite easy, the lobar holoprosencephaly is more complicated.

After a safe prenatal diagnosis, the expectant parents can decide to have an abortion on medical indications or be set by the knowledge of the birth of the child and make appropriate preparations ( hospital choice, etc.).

Nachgeburtlich the cross-sectional imaging sonography, magnetic resonance imaging and computed tomography ( CT) have proven to be a diagnostic agent.

Therapy and Follow

There is currently no known treatment, only the symptoms can be optionally treated (symptomatic therapy). The mortality rate in affected children is very high during pregnancy. The prognosis for life expectancy and development of newborn infants with holoprosencephaly is usually detrimental: Children with a severe form of malformation usually die within the first months after birth.

The prognosis is worse in the alobaren form as in the semilobaren or lobaren form. However, experience is that about 9 out of 10 children die with the alobaren form within the first year of life. Children who survive the first year, the adult can reach quite. For them, cognitive and physical impairments are depending on the severity and expected neurological abnormalities (eg, epilepsy), lack of or limited oral language development, difficulty sleeping, among others