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<!-- EDIT BELOW THIS LINE -->{{Infobox medical condition (new)|name=Achalasia Microcephaly|image=[[File:Achalasia2010.jpg|thumb|300px|Achalasia2010]]|alt=Chest x-ray of an individual with achalasia. The arrows point to the areas of extreme esophageal dilation.|caption=Chest x-ray of an individual with achalasia. The arrows point to the areas of extreme esophageal dilation.|symptoms=Manifestation of achalasia: regurgitation, vomiting and dysphagia, alongside diagnosis of microcephaly: abnormally small head size below the third percentile as well as mild to moderate mental retardation.|frequency=This constellation of symptoms has only been captured in 5 cases, affecting 9 children, between 1980-2017.|image_size=}} |
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== Achalasia Microcephaly == |
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{{See also|Esophageal achalasia|Microcephaly}} |
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<br /> |
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[[File:Microcephaly-comparison-500px.jpg|link=https://en.wikipedia.org/wiki/File:Microcephaly-comparison-500px.jpg|thumb|A comparison between the approximate head size of a baby with microcephaly (left) and a normal disposition (right). |357x357px|alt=]] |
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Achalasia Microcephaly syndrome is a rare condition whereby achalasia in the oesophagus manifests alongside microcephaly and mental retardation. This is a rare constellation of symptoms with a predicted familial trend<ref name=":0">{{Cite journal|last=Gockel|first=Henning R.|last2=Schumacher|first2=Johannes|last3=Gockel|first3=Ines|last4=Lang|first4=Hauke|last5=Haaf|first5=Thomas|last6=Nöthen|first6=Markus M.|date=2010-08-11|title=Achalasia: will genetic studies provide insights?|url=http://dx.doi.org/10.1007/s00439-010-0874-8|journal=Human Genetics|volume=128|issue=4|pages=353–364|doi=10.1007/s00439-010-0874-8|issn=0340-6717}}</ref>. |
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The main signs of achalasia microcephaly syndrome involve the manifestation of each individual disease associated with the condition. [[Microcephaly]] can be primary, where the brain fails to develop properly during pregnancy, or secondary, where the brain is normal sized at birth but fails to grow as the child ages<ref name=":3">{{Cite journal|last=Woods|first=C Geoffrey|date=2004|title=Human microcephaly|url=http://dx.doi.org/10.1016/j.conb.2004.01.003|journal=Current Opinion in Neurobiology|volume=14|issue=1|pages=112–117|doi=10.1016/j.conb.2004.01.003|issn=0959-4388|via=}}</ref>. Abnormalities will be observed progressively after birth whereby the child will display stunted growth and physical and cognitive development. The occipital-frontal circumference will be at or near the extreme lower end, the third percentile, indicating microcephaly<ref name=":1">{{Cite journal|last=Khalifa|first=M.M.|date=1988|title=Familial Achalasia, Microcephaly, and Mental Retardation|url=http://dx.doi.org/10.1177/000992288802701009|journal=Clinical Pediatrics|volume=27|issue=10|pages=509–512|doi=10.1177/000992288802701009|issn=0009-9228|via=}}</ref>. There are both genetic and behavioural causes of microcephaly<ref name=":3" />. |
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Achalasia, or [[Esophageal achalasia|oesophageal achalasia]], is a disorder occurring in the lower oesophageal sphincter (LES). The LES fails to relax completely, resulting in frequent vomiting and regurgitation, usually one to two hours after meals<ref name=":2">{{Cite journal|last=Spiess|first=Anita E.|last2=Kahrilas|first2=Peter J.|date=1998-08-19|title=Treating Achalasia|url=http://dx.doi.org/10.1001/jama.280.7.638|journal=JAMA|volume=280|issue=7|pages=638|doi=10.1001/jama.280.7.638|issn=0098-7484}}</ref><ref name=":1" />. If untreated, the long-term health of the individual will be compromised, leading to the development of dysphagia, weight loss and chronic aspiration<ref name=":2" />. It is very rare in children, especially siblings. Mortality, especially in young children, can occur<ref name=":1" />. |
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As of 2017, there are 5 reported cases of achalasia microcephaly syndrome, all of which involve children<ref name=":5">{{Cite journal|last=Wafik|first=Mohamed|last2=Kini|first2=Usha|date=2017|title=Achalasia–microcephaly syndrome: a further case report|url=http://insights.ovid.com/crossref?an=00019605-201707000-00014|journal=Clinical Dysmorphology|language=en|volume=26|issue=3|pages=190–192|doi=10.1097/MCD.0000000000000181|issn=0962-8827|via=}}</ref>. |
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== Signs and Symptoms == |
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The main symptoms of achalasia microcephaly syndrome are the progressive manifestation of the major symptoms associated with the individual diseases, in young children. |
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Achalasia causes dysphagia, which leads to difficulties when eating, frequent vomiting after meals and possible respiratory arrest due to chronic aspiration<ref name=":2" /><ref name=":4">{{Cite journal|last=Kreuz|first=Friedmar R.|last2=Nolte-Buchholtz|first2=Silke|last3=Fackler|first3=Florian|last4=Behrens|first4=Rolf|date=1999|title=Another case of achalasia-microcephaly syndrome|url=http://dx.doi.org/10.1097/00019605-199910000-00012|journal=Clinical Dysmorphology|volume=8|issue=4|pages=295???298|doi=10.1097/00019605-199910000-00012|issn=0962-8827|via=}}</ref><ref name=":5" />. Symptoms can manifest at ages as young as six weeks<ref name=":5" />. |
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Alongside prominent dysphagia, the child will have microcephaly, which is characterised by an abnormally small head. Mild scaphocephaly may also be observed<ref name=":1" /> . This can manifest upon or after birth<ref name=":3" />. Slow cognitive and fine motor development as well as delayed speech will be observed<ref name=":1" /><ref name=":5" />. Craniofacial dysmorphism, such as a globular-shaped nose, micrognathia and a flattened forehead may also be involved, but is not observed in all cases<ref name=":4" /><ref name=":5" />. Camptodactyly of some fingers can also manifest<ref name=":7">{{Cite journal|last=Hernández|first=Alejandro|last2=Reynoso|first2=Martha Celina|last3=Soto|first3=Fernando|last4=Quiñones|first4=David|last5=Nazará|first5=Zamira|last6=Fragoso|first6=Ruben|date=1989|title=Achalasia microcephaly syndrome in a patient with consanguineous parents: support for a.m. being a distinct autosomal recessive condition|url=http://dx.doi.org/10.1111/j.1399-0004.1989.tb03376.x|journal=Clinical Genetics|volume=36|issue=6|pages=456–458|doi=10.1111/j.1399-0004.1989.tb03376.x|issn=|pmid=2591072|via=}}</ref>. |
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== Etiology == |
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Achalasia microcephaly has only been reported in children, despite achalasia being associated as an adult disease<ref name=":1" />. |
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The first case involved an affected family of four children, three sisters and one brother, from northwest Mexico<ref>{{Cite journal|last=Williams|first=J J|last2=Sandin|first2=C S|last3=Dumars|first3=K W|date=1978|title=New syndrome: microcephaly associated with achalasia|url=|journal=American Journal of Human Genetics|volume=30|pages=106|via=}}</ref><ref name=":10">{{Cite journal|last=Dumars|first=Kenneth W.|last2=Williams|first2=James J.|last3=Steele-Sandlin|first3=Constance|last4=|first4=|date=1980|title=Achalasia and microcephaly|url=http://dx.doi.org/10.1002/ajmg.1320060408|journal=American Journal of Medical Genetics|volume=6|issue=4|pages=309–314|doi=10.1002/ajmg.1320060408|issn=0148-7299|pmid=7211947|via=}}</ref>. All three sisters underwent the [[Heller myotomy|Heller procedure]] in order to relieve vomiting and regurgitation due to achalasia. The brother passed away at four and a half years old<ref name=":10" />, due to the improper diagnosis of recurrent vomiting and resultant malnourishment. All siblings had slow to moderate cognitive development within the mentally retarded criteria. Both parents were unaffected and were from the same small village. |
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The second case involved two affected brothers, aged seven and nine, from Libya, in a family of six children<ref name=":1" />. By the age of two, both children were vomiting and regurgitating recurrently, had slow development and suffered from pneumonitis. They also displayed mild micrognathia and scaphocephaly<ref name=":1" />. The elder son underwent a modified Heller’s operation at age six. Their parents were first cousins, however, chromosomal studies did not observe any abnormalities<ref name=":1" />. |
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The third examined case was an affected nine-year-old boy born to unaffected parents who were from the same north-western Mexican area as the first reported case<ref name=":7" />. It is denied but implicated that the parents were closely related. Abnormalities in motor function, physical appearance and difficulties during feeding manifested after birth<ref name=":7" />. By eight months, psychomotor retardation was prominent and at nine months, malnourishment was extreme and so oesophagomyotomy ([[Heller myotomy]]) was performed<ref name=":7" />. At eighteen months, microcephaly was revealed<ref name=":7" />. |
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The fourth case study involved an affected German child<ref name=":4" />. Unlike previous cases, the condition was attributed to the anti-malaria drug, Mefloquine, which was prescribed during pregnancy. There is no apparent genetic correlation between parents<ref name=":4" />. At eight weeks, the child was officially diagnosed with microcephaly and displayed craniofacial dysmorphism and muscular hypotonia similar to previous cases. Vomiting, seizures and respiratory arrest were common. It was noted that only 5.4% of pregnancies under the medication of Mefloquine experienced abnormalities<ref name=":4" />. This is the first case involving a person of European descent. |
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The fifth, most recent case, involved a girl born to consanguineous parents from Pakistan. There was no history of abnormalities or genetic disorders in previous children in the family<ref name=":5" />. Gestational diabetes during the pregnancy did not cause any significant complications. Feeding difficulties and recurrent vomiting began to occur at six weeks, resulting in severe weight loss<ref name=":5" />. The girl received surgery and repeated balloon dilatations by the age of two for severe achalasia. She was diagnosed with microcephaly at age six after concerns for her delayed fine motor skills and limited understanding of speech<ref name=":5" />. |
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== Mechanism == |
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Achalasia is a neurodegenerative disease characterised by the degeneration of neurones of the myenteric plexus which are responsible for the motility of the digestive tract<ref name=":8">{{Cite journal|last=Gockel|first=Ines|last2=Müller|first2=Michaela|last3=Schumacher|first3=Johannes|date=2012-03-23|title=Achalasia|url=https://www.aerzteblatt.de/10.3238/arztebl.2012.0209|journal=Deutsches Aerzteblatt Online|doi=10.3238/arztebl.2012.0209|issn=1866-0452|pmc=PMC3329145|pmid=22532812}}</ref>. It is extremely rare in children and normally affects the lower oesophageal sphincter (LES)<ref name=":5" /><ref name=":8" />. LES contraction prevents acid reflux while relaxation allows food to enter the stomach<ref name=":8" />. Impaired LES relaxation therefore leads to dysphagia, as the oesophagus cannot be emptied<ref name=":8" />. Familial achalasia, whereby achalasia manifests among siblings, is noted in families displaying consanguinity or inbreeding as the disease can be passed on as an autosomal recessive trait<ref>{{Cite journal|last=Monnig|first=P.J.|date=1990|title=Familial achalasia in children|url=http://dx.doi.org/10.1016/0003-4975(90)90897-f|journal=The Annals of Thoracic Surgery|volume=49|issue=6|pages=1019–1022|doi=10.1016/0003-4975(90)90897-f|issn=0003-4975|via=}}</ref>. |
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Microcephaly can manifest due to a variety of reasons, these include: [[TORCH syndrome|TORCH]] infections, chromosomal and biochemical abnormalities and can be transmitted as an autosomal recessive, dominant or X-linked disorder<ref name=":10" />. It is most commonly caused by congenital infections due to viruses such as cytomegalovirus, herpes simplex virus and Zika virus<ref name=":9">{{Cite journal|last=Devakumar|first=Delan|last2=Bamford|first2=Alasdair|last3=Ferreira|first3=Marcelo U|last4=Broad|first4=Jonathan|last5=Rosch|first5=Richard E|last6=Groce|first6=Nora|last7=Breuer|first7=Judith|last8=Cardoso|first8=Marly A|last9=Copp|first9=Andrew J|date=2018|title=Infectious causes of microcephaly: epidemiology, pathogenesis, diagnosis, and management|url=http://dx.doi.org/10.1016/s1473-3099(17)30398-5|journal=The Lancet Infectious Diseases|volume=18|issue=1|pages=e1–e13|doi=10.1016/s1473-3099(17)30398-5|issn=1473-3099|via=}}</ref>. The severe reduction of neural progenitors and neurones as a result of cell cycle arrest and neural progenitor death due to viral infection leads to microcephaly<ref name=":9" />. There are two types of microcephaly, primary, occurring before thirty-two weeks of gestation or secondary, after birth<ref name=":3" />. A reduced production of neurones is attributed to primary microcephaly whilst decreased dendritic connection is thought to cause secondary microcephaly, all amounting to an estimated brain size that is significantly smaller than average<ref name=":3" />. Further, the cerebral cortex occupies 55% of the human brain, therefore, most microcephalic people are mentally retarded<ref name=":3" />. <ref name=":2" />. |
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Like familial achalasia, microcephaly has an autosomal recessive predisposition<ref name=":9" />. |
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Although no disease-causing gene has been identified, studies suggest that due to the consanguinity or close relatedness of parents observed in four out of five cases, achalasia microcephaly might be inherited via an autosomal recessive gene<ref name=":0" /><ref name=":7" />. |
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== Diagnosis == |
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[[File:Normal barium swallow animation.gif|thumb|Barium swallow procedure commonly used for the diagnosis of achalasia. |349x349px]] |
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Symptoms of achalasia can be detected by fluoroscopy during [[barium swallow]] or [[esophageal manometry|oesophageal manometry]]<ref name=":2" />. |
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=== Achalasia === |
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==== Barium Swallow ==== |
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A positive barium swallow with display aperistalsis, minimal LES opening and oesophageal dilation as the main indicator of the disease<ref name=":2" />. |
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==== Oesophageal Manometry ==== |
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Patients who suffer from the vigorous achalasia variant of the disease, do not express dilation<ref name=":2" />. Manometry is the best, most sensitive method in these cases as it can diagnose abnormalities related to achalasia without dilation<ref name=":2" />. |
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=== Microcephaly === |
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Microcephaly is usually diagnosed after the onset of achalasia by eighteen months or older<ref name=":7" />. An occipital-frontal head circumference of less than three standard deviations is an indication of microcephaly<ref name=":3" />. Radiography and NMR imaging of the skull can also be utilised<ref name=":4" />. A physical examination of height and weight proportions as well as IQ and motor development is implemented for further confirmation as not all children with microcephaly have abnormal development<ref name=":1" /><ref name=":9" />. A positive test will show normal to abnormal proportions, a low IQ and slow motor development. |
|||
== Management == |
|||
There is currently no treatment to reverse the neuropathology of achalasia or the effects of microcephaly. |
|||
Instead, treatment for achalasia symptoms focuses on the reduction of LES pressure to relieve dysphagia and therefore prevent further regurgitation, vomiting and aspiration<ref name=":2" />. These include drugs such as anticholinergics, mechanical dilation with a balloon dilator, or heller myotomy surgery<ref name=":2" /><ref name=":5" />. |
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Exogenous growth hormones can be used to boost development in microcephalic patients<ref>{{Cite journal|last=Spadoni|first=Gian Luigi|last2=Cianfarani|first2=Stefano|last3=Bernardini|first3=Sergio|date=1989|title=Growth Hormone Treatment in Children With Sporadic Primary Microcephaly|url=http://dx.doi.org/10.1001/archpedi.1989.02150230040019|journal=Archives of Pediatrics & Adolescent Medicine|volume=143|issue=11|pages=1282-1283|doi=10.1001/archpedi.1989.02150230040019|issn=1072-4710|via=}}</ref>. |
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== Research == |
|||
No disease causing gene for achalasia microcephaly has been found, however candidate genes for research include genes that are known to be associated with the individual diseases that manifest alongside achalasia<ref name=":0" />. Studies implicate that biological disturbances in the pathways downstream of these candidate genes can lead to the development of achalasia<ref name=":0" />. |
|||
It is suggested that the disease has roots in neurological dysfunction due to the co-occurrence of microcephaly, the progressive narrowing of the oesophagus in the early stages of life and intellectual disability<ref name=":5" />. Whole-exosome and whole-genome sequencing is proposed for the discovery of the underlying genetic cause of achalasia microcephaly<ref name=":5" />. |
|||
The familial trend of disease manifestation between siblings along with consanguinity in majority of cases is consistent with an autosomal recessive inheritance<ref name=":10" /><ref name=":1" />. |
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== References == |
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<references />{{Medicine}}{{Thoracic surgery}}{{Congenital malformations and deformations of nervous system}} |
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Latest revision as of 10:49, 8 May 2019
| Achalasia Microcephaly | |
|---|---|
 | |
| Chest x-ray of an individual with achalasia. The arrows point to the areas of extreme esophageal dilation. | |
| Symptoms | Manifestation of achalasia: regurgitation, vomiting and dysphagia, alongside diagnosis of microcephaly: abnormally small head size below the third percentile as well as mild to moderate mental retardation. |
| Frequency | This constellation of symptoms has only been captured in 5 cases, affecting 9 children, between 1980-2017. |
Achalasia Microcephaly
[edit]
Achalasia Microcephaly syndrome is a rare condition whereby achalasia in the oesophagus manifests alongside microcephaly and mental retardation. This is a rare constellation of symptoms with a predicted familial trend[1].
The main signs of achalasia microcephaly syndrome involve the manifestation of each individual disease associated with the condition. Microcephaly can be primary, where the brain fails to develop properly during pregnancy, or secondary, where the brain is normal sized at birth but fails to grow as the child ages[2]. Abnormalities will be observed progressively after birth whereby the child will display stunted growth and physical and cognitive development. The occipital-frontal circumference will be at or near the extreme lower end, the third percentile, indicating microcephaly[3]. There are both genetic and behavioural causes of microcephaly[2].
Achalasia, or oesophageal achalasia, is a disorder occurring in the lower oesophageal sphincter (LES). The LES fails to relax completely, resulting in frequent vomiting and regurgitation, usually one to two hours after meals[4][3]. If untreated, the long-term health of the individual will be compromised, leading to the development of dysphagia, weight loss and chronic aspiration[4]. It is very rare in children, especially siblings. Mortality, especially in young children, can occur[3].
As of 2017, there are 5 reported cases of achalasia microcephaly syndrome, all of which involve children[5].
Signs and Symptoms
[edit]The main symptoms of achalasia microcephaly syndrome are the progressive manifestation of the major symptoms associated with the individual diseases, in young children.
Achalasia causes dysphagia, which leads to difficulties when eating, frequent vomiting after meals and possible respiratory arrest due to chronic aspiration[4][6][5]. Symptoms can manifest at ages as young as six weeks[5].
Alongside prominent dysphagia, the child will have microcephaly, which is characterised by an abnormally small head. Mild scaphocephaly may also be observed[3] . This can manifest upon or after birth[2]. Slow cognitive and fine motor development as well as delayed speech will be observed[3][5]. Craniofacial dysmorphism, such as a globular-shaped nose, micrognathia and a flattened forehead may also be involved, but is not observed in all cases[6][5]. Camptodactyly of some fingers can also manifest[7].
Etiology
[edit]Achalasia microcephaly has only been reported in children, despite achalasia being associated as an adult disease[3].
The first case involved an affected family of four children, three sisters and one brother, from northwest Mexico[8][9]. All three sisters underwent the Heller procedure in order to relieve vomiting and regurgitation due to achalasia. The brother passed away at four and a half years old[9], due to the improper diagnosis of recurrent vomiting and resultant malnourishment. All siblings had slow to moderate cognitive development within the mentally retarded criteria. Both parents were unaffected and were from the same small village.
The second case involved two affected brothers, aged seven and nine, from Libya, in a family of six children[3]. By the age of two, both children were vomiting and regurgitating recurrently, had slow development and suffered from pneumonitis. They also displayed mild micrognathia and scaphocephaly[3]. The elder son underwent a modified Heller’s operation at age six. Their parents were first cousins, however, chromosomal studies did not observe any abnormalities[3].
The third examined case was an affected nine-year-old boy born to unaffected parents who were from the same north-western Mexican area as the first reported case[7]. It is denied but implicated that the parents were closely related. Abnormalities in motor function, physical appearance and difficulties during feeding manifested after birth[7]. By eight months, psychomotor retardation was prominent and at nine months, malnourishment was extreme and so oesophagomyotomy (Heller myotomy) was performed[7]. At eighteen months, microcephaly was revealed[7].
The fourth case study involved an affected German child[6]. Unlike previous cases, the condition was attributed to the anti-malaria drug, Mefloquine, which was prescribed during pregnancy. There is no apparent genetic correlation between parents[6]. At eight weeks, the child was officially diagnosed with microcephaly and displayed craniofacial dysmorphism and muscular hypotonia similar to previous cases. Vomiting, seizures and respiratory arrest were common. It was noted that only 5.4% of pregnancies under the medication of Mefloquine experienced abnormalities[6]. This is the first case involving a person of European descent.
The fifth, most recent case, involved a girl born to consanguineous parents from Pakistan. There was no history of abnormalities or genetic disorders in previous children in the family[5]. Gestational diabetes during the pregnancy did not cause any significant complications. Feeding difficulties and recurrent vomiting began to occur at six weeks, resulting in severe weight loss[5]. The girl received surgery and repeated balloon dilatations by the age of two for severe achalasia. She was diagnosed with microcephaly at age six after concerns for her delayed fine motor skills and limited understanding of speech[5].
Mechanism
[edit]Achalasia is a neurodegenerative disease characterised by the degeneration of neurones of the myenteric plexus which are responsible for the motility of the digestive tract[10]. It is extremely rare in children and normally affects the lower oesophageal sphincter (LES)[5][10]. LES contraction prevents acid reflux while relaxation allows food to enter the stomach[10]. Impaired LES relaxation therefore leads to dysphagia, as the oesophagus cannot be emptied[10]. Familial achalasia, whereby achalasia manifests among siblings, is noted in families displaying consanguinity or inbreeding as the disease can be passed on as an autosomal recessive trait[11].
Microcephaly can manifest due to a variety of reasons, these include: TORCH infections, chromosomal and biochemical abnormalities and can be transmitted as an autosomal recessive, dominant or X-linked disorder[9]. It is most commonly caused by congenital infections due to viruses such as cytomegalovirus, herpes simplex virus and Zika virus[12]. The severe reduction of neural progenitors and neurones as a result of cell cycle arrest and neural progenitor death due to viral infection leads to microcephaly[12]. There are two types of microcephaly, primary, occurring before thirty-two weeks of gestation or secondary, after birth[2]. A reduced production of neurones is attributed to primary microcephaly whilst decreased dendritic connection is thought to cause secondary microcephaly, all amounting to an estimated brain size that is significantly smaller than average[2]. Further, the cerebral cortex occupies 55% of the human brain, therefore, most microcephalic people are mentally retarded[2]. [4].
Like familial achalasia, microcephaly has an autosomal recessive predisposition[12].
Although no disease-causing gene has been identified, studies suggest that due to the consanguinity or close relatedness of parents observed in four out of five cases, achalasia microcephaly might be inherited via an autosomal recessive gene[1][7].
Diagnosis
[edit]
Symptoms of achalasia can be detected by fluoroscopy during barium swallow or oesophageal manometry[4].
Achalasia
[edit]Barium Swallow
[edit]A positive barium swallow with display aperistalsis, minimal LES opening and oesophageal dilation as the main indicator of the disease[4].
Oesophageal Manometry
[edit]Patients who suffer from the vigorous achalasia variant of the disease, do not express dilation[4]. Manometry is the best, most sensitive method in these cases as it can diagnose abnormalities related to achalasia without dilation[4].
Microcephaly
[edit]Microcephaly is usually diagnosed after the onset of achalasia by eighteen months or older[7]. An occipital-frontal head circumference of less than three standard deviations is an indication of microcephaly[2]. Radiography and NMR imaging of the skull can also be utilised[6]. A physical examination of height and weight proportions as well as IQ and motor development is implemented for further confirmation as not all children with microcephaly have abnormal development[3][12]. A positive test will show normal to abnormal proportions, a low IQ and slow motor development.
Management
[edit]There is currently no treatment to reverse the neuropathology of achalasia or the effects of microcephaly.
Instead, treatment for achalasia symptoms focuses on the reduction of LES pressure to relieve dysphagia and therefore prevent further regurgitation, vomiting and aspiration[4]. These include drugs such as anticholinergics, mechanical dilation with a balloon dilator, or heller myotomy surgery[4][5].
Exogenous growth hormones can be used to boost development in microcephalic patients[13].
Research
[edit]No disease causing gene for achalasia microcephaly has been found, however candidate genes for research include genes that are known to be associated with the individual diseases that manifest alongside achalasia[1]. Studies implicate that biological disturbances in the pathways downstream of these candidate genes can lead to the development of achalasia[1].
It is suggested that the disease has roots in neurological dysfunction due to the co-occurrence of microcephaly, the progressive narrowing of the oesophagus in the early stages of life and intellectual disability[5]. Whole-exosome and whole-genome sequencing is proposed for the discovery of the underlying genetic cause of achalasia microcephaly[5].
The familial trend of disease manifestation between siblings along with consanguinity in majority of cases is consistent with an autosomal recessive inheritance[9][3].
References
[edit]- ^ a b c d Gockel, Henning R.; Schumacher, Johannes; Gockel, Ines; Lang, Hauke; Haaf, Thomas; Nöthen, Markus M. (2010-08-11). "Achalasia: will genetic studies provide insights?". Human Genetics. 128 (4): 353–364. doi:10.1007/s00439-010-0874-8. ISSN 0340-6717.
- ^ a b c d e f g Woods, C Geoffrey (2004). "Human microcephaly". Current Opinion in Neurobiology. 14 (1): 112–117. doi:10.1016/j.conb.2004.01.003. ISSN 0959-4388.
- ^ a b c d e f g h i j k Khalifa, M.M. (1988). "Familial Achalasia, Microcephaly, and Mental Retardation". Clinical Pediatrics. 27 (10): 509–512. doi:10.1177/000992288802701009. ISSN 0009-9228.
- ^ a b c d e f g h i j Spiess, Anita E.; Kahrilas, Peter J. (1998-08-19). "Treating Achalasia". JAMA. 280 (7): 638. doi:10.1001/jama.280.7.638. ISSN 0098-7484.
- ^ a b c d e f g h i j k l Wafik, Mohamed; Kini, Usha (2017). "Achalasia–microcephaly syndrome: a further case report". Clinical Dysmorphology. 26 (3): 190–192. doi:10.1097/MCD.0000000000000181. ISSN 0962-8827.
- ^ a b c d e f Kreuz, Friedmar R.; Nolte-Buchholtz, Silke; Fackler, Florian; Behrens, Rolf (1999). "Another case of achalasia-microcephaly syndrome". Clinical Dysmorphology. 8 (4): 295???298. doi:10.1097/00019605-199910000-00012. ISSN 0962-8827.
- ^ a b c d e f g Hernández, Alejandro; Reynoso, Martha Celina; Soto, Fernando; Quiñones, David; Nazará, Zamira; Fragoso, Ruben (1989). "Achalasia microcephaly syndrome in a patient with consanguineous parents: support for a.m. being a distinct autosomal recessive condition". Clinical Genetics. 36 (6): 456–458. doi:10.1111/j.1399-0004.1989.tb03376.x. PMID 2591072.
- ^ Williams, J J; Sandin, C S; Dumars, K W (1978). "New syndrome: microcephaly associated with achalasia". American Journal of Human Genetics. 30: 106.
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