Which Drug Can Cause Moebius Syndrome & Is There A Cure For It?

About Moebius Syndrome.

Moebius syndrome is a neurological disorder which was found out by a German neurologist, Paul Julius Moebius, and is thus named as ‘Moebius syndrome’. While the exact cause is not known, it is believed that this condition can be caused by intake of a drug. This article discusses about which drug can cause Moebius syndrome and if there is any cure for it.

People suffering from Moebius syndrome can be identified by their external appearance of the face and limbs. The main features of the patients with Moebius syndrome are, micrognathia (reduced size of chin), microstomia (small mouth), cleft palate (the roof of mouth and lip is split), abnormalities in the teeth, abnormalities in the eye (including difficulty in closing the eyelids, strabismus, unable to make eye contact), abnormalities in the bone and the infants with Moebius syndrome show slow motor skills.

Though the exact reason for Moebius syndrome is yet to be known, there have been attempts to find out the causes. Some records show that genetic and environmental factors play a major role in causing this syndrome. Some researches show that Moebius syndrome might also have been caused by usage of some drugs during pregnancy particularly in early period of gestation say at 6 to 8 weeks.

Which Drug Can Cause Moebius Syndrome?

It is believed that some drugs can cause Moebius syndrome. If a pregnant woman of 6 to 8 weeks of gestation takes cocaine, ergot compounds, misoprostol and/or thalidomide; it is found that the child, if survives, would get congenital diseases. The phenomenon of getting congenital diseases including mental and physical retardation, sometimes with or without malformations of the structure is called teratogenicity. One such congenital disease is Moebius syndrome. So, which drug can cause Moebius syndrome? We shall study the usage and adverse effects of wrong usage of these drugs one by one.

Cocaine Being a Cause of Moebius Syndrome.

Cocaine is an organic compound called Benzoylmethylecgonine It is a crystalline powder, with white color and a volatile substance with low melting point. Cocaine is soluble in water. It can be found in two forms, one is pure form and another cocaine hydrochloride. It is mostly used as a free base by removing hydrochloride salt and thus becomes a water insoluble substance. Cocaine is prepared from a plant called coca. The native of this plant is South America. Some of the other names of cocaine are blow, coke crack, rock, snow, etc. As cocaine can be a drug the can cause Moebius syndrome, it is necessary to study its effects on human body.

Cocaine is found to interfere with the process of rewarding of some neurotransmitters like dopamine. This results in accumulation of neurotransmitters in the brain and the person feels high in an unnatural way. This also inhibits further uptake of neurotransmitters particularly dopamine. Thus, the person who uses it becomes addicted. Cocaine stimulates the nervous system and is a psychoactive drug. Usage of this drug for recreation purpose is considered as drug abuse as it causes addiction.

The euphoric effects of cocaine are a feel of highness, high energy, fatigue is reduced, mental alertness is increased and because of this the abused person has loss of sleep. The individuals become too talkative on usage, do not feel hungry and behave like an extravert because of elevated mood.

The way in which cocaine drug can cause Moebius syndrome relates to the way in which it affects during pregnancy and the child in the womb. The multiple ways in which the fetus or the baby can be affected if the mother abuses cocaine are.

In blood plasma there are some types pf esterase called serum cholinesterase which can degrade the cocaine. Instead, the cocaine reduces the quantity of serum cholinesterase and checks its function thereby causing the following problems on the woman; rupture of membrane in the early stage itself, before the delivery, the placenta gets separated from the wall of uterus, spontaneous bleeding with abortion, migraines, seizures, hypertension which induces activity of uterus, birth of premature baby, either the woman suffers from miscarriage and/or the delivery becomes difficult.

On the other hand, though the health and birth of the child depends on several factors like socioeconomic conditions, environment, lifestyle, maternal stress and tensions; usage of cocaine during pregnancy plays a major role in deciding the condition of the baby. It is found to cause many congenital diseases in the fetus including Moebius syndrome. The presence of cocaine in the pregnant woman’s body restricts the blood circulation to the fetus which affects the development of different organs of the body of fetus. Most affected parts due to the presence of cocaine in mother’s body are brain (causing microcephaly), intestine, kidneys and heart. Many children might also have cleft lip with cleft palate, polydactyly, etc.

Cocaine is a teratogenic substance which causes impairments in neurons of the unborn babies and also of the infants. Usage of cocaine by pregnant women inhibits the activity of neurotransmitter which is responsible for attention and visual memories, thus causing memory loss, lack of attention, reduction in intellectual capacity. The children of mothers who used cocaine in pregnancy show less response to the external stimuli.

Using cocaine in pregnancy checks the activity of a protein responsible for cell division called cyclin A which in turn reduces the development of neurons and brain of fetus.
Malnutrition is another hindrance for the normal development of fetus causing low birth weight of baby in women who took cocaine in pregnancy.

Ergot Drug and its Contribution Towards the Occurrence of Moebius Syndrome.

Ergot belongs to a group of fungi which grows commonly on rye. It contains water soluble alkaloids of ergometrine group and water insoluble of ergotamine group compounds. It causes ergotism in humans, an unhealthy condition which is symptomized by spasms, paresthesia, itching, nausea, headaches, gangrene, etc. Ergot too is a drug that can cause Moebius syndrome and its usage and effects are as follows.

Medical Use of ergot derivatives. Generally, ergot derivatives in the form of dihydroergotamine and ergotamine were used to address throbbing headaches such as migraine. The combination of it and caffeine is found to relieve these headaches, aid in relaxation and good sleep.

Effect of Ergot Derivatives on Pregnant Women and her Child causing Moebius Syndrome. Though there is not much research on improving health conditions in problems related to menstruation and menopause, some women used to take this as medicine to minimize bleeding during the above mentioned situations. Ergot drugs are found to reduce bleeding by constricting blood vessels. It was also used to reduce bleeding before and after miscarriage. In cases where the expulsion of placenta was found difficult, this ergot drug was used to facilitate easy expulsion. It is an unsafe drug. The complications of using this drug include weakness, muscle pain, nausea and/or vomiting, unconsciousness, spasms, variation in heartbeat, mental confusion and lastly death. Usage of ergot drug is not safe; it causes many serious and harmful effects on pregnant women who consume it and even on the unborn child. There are chances of occurrence of Moebius syndrome to the children of women who are treated with ergot derivatives during pregnancy.

Misoprostol and Moebius Syndrome.

Chemical name of misoprostol is methyl7 ((1R, 2R, 3R)-3-hydroxy -2-((S, E)-4-hydroxy-4-methylocto-1-enyl)-5-oxocyclopentyl) heptanoate. Some of the trade names are misodel, cytotec, etc. Let us understand the effects of Misoprostol to understand how the drug can cause Moebius syndrome.

Medical Uses and Side Effects of Misoprostol. Misoprostol is used for many purposes. It is used to treat patients with stomach ulcers (individuals who take NSAIDs are more prone to get stomach ulcers), reduce diarrhea, abortion, to start labor. The side effects of misoprostol include dehydration, reduced frequency of urination, mood swings, dizziness, weakness, irregular heartbeat, etc.

Effect of Misoprostol on Pregnant Woman and her Child by Causing Moebius Syndrome. If this medicine is taken by a pregnant woman to end pregnancy in combination with mifepristone, she has to be very careful and should be under keen supervision by the doctor. During pregnancy, misoprostol should never be taken for stomach ulcers. In case if it is taken, it may lead to abortion. Misoprostol causes contraction of uterus leading to bleeding. This can cause disruption in blood supply to the placenta. It gradually leads to hypoxia, hypoperfusion and supply of oxygen to the fetus is cut off finally causing abortion. In case if the baby survives, the unborn baby would be at risk of getting congenital diseases including Moebius syndrome. Even records are available for the presence of misoprostol in breast milk but are not found to cause any harm to the infant.

Thalidomide and Moebius Syndrome.

Thalidomide also known as α – (N-phthalimido) glutarimide is a piperidinyl isoindole, also a derivative of glutamic acid. Molecular formula of thalidomide is C13H10N2O4 and its molecular weight is 258.233 g/mol. The general properties of this drug are – it acts as antiangiogenic, immunomodulatory, anti-inflammatory and also has teratogenic property. Here are the ways in which this drug can cause Moebius syndrome.

Medical Uses of Thalidomide. It is a sedative and hence thought to help in conditions like anxiety, tension, insomnia and also gastritis. Thalidomide is used to treat many diseases like Hansen’s disease. It works in multiple myeloma, a kind of cancer by checking the supply of blood to the tumors. Sometimes, it is used to reduce brain inflammation by the doctors if they find corticosteroids are insufficient.

Side Effects of Thalidomide. There are some adverse effects of thalidomide too. Sometimes, thalidomide acts as a barrier for the formation of new blood cells causing lymphopenia, neutropenia and also leucopenia. It is found to increase bleeding because of the formation of thrombocytopenia. Problems with heart, hypertension, decreased blood supply to the brain, bradycardia, liver damage, numbness, tremor, constipation, dizziness, peripheral edema, tingling, severe permanent nerve damage, etc., are also listed as the adverse effects of thalidomide drug.

Effects of Usage of Thalidomide on Pregnant Women and the Fetus. As mentioned earlier, it induces teratogenesis in the fetus. Hence, it must be strictly avoided by the pregnant women. Congenital diseases like Moebius syndrome is reported in the child of a mother who was exposed to thalidomide during her early stages of pregnancy. The way it interferes the development of embryo can be well explained. There are many defense mechanisms in the embryos which include prevention of entry of toxic substances and/or removing the same from the embryonic cells. This is done by efflux transportation system which involves ATP binding Cassette proteins. These proteins recognize the toxins and chemicals, bind to them and remove them. Thalidomide on the other hand escapes from recognition by these proteins and would be within the cell. Reactive Oxygen Species dependent signaling pathways are disturbed due to oxidative stress caused by thalidomide. These pathways are responsible for growth of limb bud. From records, it can be stated that multiple body systems were also affected by thalidomide. It also increases the chances of miscarriage. Records also give us information that if the child is survived even after the expecting mother is exposed to thalidomide, the child would be severely handicapped. Though there are no effective evidences of presence of thalidomide in breast milk, breast feeding during the usage of this drug is also avoided.

Is There a Cure for Moebius Syndrome?

Unfortunately, there is no cure for Moebius syndrome. The treatment provided is supportive and symptomatic management. To maintain the nutrition level and to prevent nutritional deficiency, a child might have to be fed through feeding tubes. Surgeries can help to correct crossed eye and to correct limb and jaw deformities. Physical therapy and speech therapy is needed to improve motor skill as well as coordination and to promote speech and eating abilities. Nerve and muscle transfer to the mouth corners can help the child in smiling. Plastic reconstructive surgery again can be beneficial for some individuals. The most important part if the prevention of this condition, as it is known that certain drugs can cause Moebius syndrome.

Conclusion

Though the causes of Moebius syndrome are many, teratogenicity because of usage of many drugs during early period of gestation is also one of the major causes. Most of the symptoms of Moebius syndrome related to face such as fasciculation of tongue, lacking facial expression, nerve palsies are concerned with the problems of Cranial nerves XI and XII. Drugs such as cocaine, misoprostol, ergot derivatives and thalidomide are the major teratogenic drugs causing congenital diseases including Moebius syndrome. The adverse effects of the above mentioned drugs on fetus when used by the mother during pregnancy including moebius syndrome are mostly irreversible and permanent. Attempts are being made to treat the symptoms and thus helping to manage the disease.

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