Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Miller-Dieker occurs in less than one in 100000 people and can occur in all races.
Most individuals with this condition do not survive beyond childhood. Individuals with MDS usually die in infancy and therefore do not live to the age where they can reproduce and transmit MDS to their offspring.
The prognosis for children with lissencephaly varies depending on the malformation. Many individuals remain in a 3–5 month developmental level. Some children with lissencephaly will be able to roll over, sit, reach for objects, and smile socially. Aspiration and respiratory disease are the most common causes of illness or death. In the past, life expectancy was said to be around two years of age. However, with advances in seizure control, and treatments for respiratory illness, most children live well beyond that age. With other advances in therapy, and the broader availability of services and equipment, some children with lissencephaly are able to walk with varying degrees of assistance and to perform other functions once thought too advanced.
Isolated
1. Familial (autosomal recessive) microcephaly
2. Autosomal dominant microcephaly
3. X-linked microcephaly
4. Chromosomal (balanced rearrangements and ring chromosome)
Syndromes
- Chromosomal
1. Poland syndrome
2. Down syndrome
3. Edward syndrome
4. Patau syndrome
5. Unbalanced rearrangements
- Contiguous gene deletion
1. 4p deletion (Wolf–Hirschhorn syndrome)
2. 5p deletion (Cri-du-chat)
3. 7q11.23 deletion (Williams syndrome)
4. 22q11 deletion (DiGeorge syndrome)
- Single gene defects
1. Smith–Lemli–Opitz syndrome
2. Seckel syndrome
3. Cornelia de Lange syndrome
4. Holoprosencephaly
5. Primary microcephaly 4
6. Wiedemann-Steiner syndrome
Acquired
- Disruptive injuries
1. Ischemic stroke
2. Hemorrhagic stroke
3. Death of a monozygotic twin
- Vertically transmitted infections
1. Congenital cytomegalovirus infection
2. Toxoplasmosis
3. Congenital rubella syndrome
4. Zika virus
- Drugs
1. Fetal hydantoin syndrome
2. Fetal alcohol syndrome
Other
1. Radiation exposure to mother
2. Maternal malnutrition
3. Maternal phenylketonuria
4. Poorly controlled gestational diabetes
5. Hyperthermia
6. Maternal hypothyroidism
7. Placental insufficiency
Microlissencephaly is listed in Orphanet database as a rare disease. There is no much information available about the epidemiology of microlissencepahly in literature. A PhD thesis has estimated the prevalence of microlissencepahly in South–Eastern Hungary between July 1992 and June 2006 to be a case every 91,000 live births (0.11:10,000).
Genetic
- Inborn errors of metabolism
1. Congenital disorder of glycosylation
2. Mitochondrial disorders
3. Peroxisomal disorder
4. Glucose transporter defect
5. Menkes disease
6. Congenital disorders of amino acid metabolism
7. Organic acidemia
Syndromes
- Contiguous gene deletion
1. 17p13.3 deletion (Miller–Dieker syndrome)
- Single gene defects
1. Rett syndrome (primarily girls)
2. Nijmegen breakage syndrome
3. X-linked lissencephaly with abnormal genitalia
4. Aicardi–Goutières syndrome
5. Ataxia telangiectasia
6. Cohen syndrome
7. Cockayne syndrome
Acquired
- Disruptive injuries
1. Traumatic brain injury
2. Hypoxic-ischemic encephalopathy
3. Ischemic stroke
4. Hemorrhagic stroke
- Infections
1. Congenital HIV encephalopathy
2. Meningitis
3. Encephalitis
- Toxins
1. Lead poisoning
2. Chronic renal failure
- Deprivation
1. Hypothyroidism
2. Anemia
3. Congenital heart disease
4. Malnutrition
Genetic factors may play a role in causing some cases of microcephaly. Relationships have been found between autism, duplications of chromosomes, and macrocephaly on one side. On the other side, a relationship has been found between schizophrenia, deletions of chromosomes, and microcephaly. Moreover, an association has been established between common genetic variants within known microcephaly genes ("MCPH1, CDK5RAP2") and normal variation in brain structure as measured with magnetic resonance imaging (MRI)i.e., primarily brain cortical surface area and total brain volume.
The spread of Aedes mosquito-borne Zika virus has been implicated in increasing levels of congenital microcephaly by the International Society for Infectious Diseases and the US Centers for Disease Control and Prevention. Zika can spread from a pregnant woman to her fetus. This can result in other severe brain malformations and birth defects. A study published in The New England Journal of Medicine has documented a case in which they found evidence of the Zika virus in the brain of a fetus that displayed the morphology of microcephaly.
Parents of a proband
- The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele.
- Heterozygotes (carriers) are asymptomatic.
Sibs of a proband
- At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
- Once an at-risk sibling is known to be unaffected, the risk of his/her being a carrier is 2/3.
- Heterozygotes (carriers) are asymptomatic.
Offspring of a proband
- Offspring of a proband are obligate heterozygotes and will therefore carry one mutant allele.
- In populations with a high rate of consanguinity, the offspring of a person with GPR56-related BFPP and a reproductive partner who is a carrier of GPR56-related BFPP have a 50% chance of inheriting two GPR56 disease-causing alleles and having BFPP and a 50% chance of being carriers.
Other family members of a proband.
- Each sibling of the proband's parents is at a 50% risk of being a carrier
The prognosis is poor; affected individuals are either stillborn or die shortly after birth. The longest survival reported in literature is of 134 days.
This syndrome is transmitted as an autosomal recessive disorder and there is a risk for recurrence of 25% in future pregnancies.
Because pachygyria is a structural defect no treatments are currently available other than symptomatic treatments, especially for associated seizures. Another common treatment is a gastrostomy (insertion of a feeding tube) to reduce possible poor nutrition and repeated aspiration pneumonia.
Microlissencephaly (MLIS) is a rare congenital brain disorder that combines severe microcephaly (small head) with lissencephaly (smooth brain surface due to absent sulci and gyri). Microlissencephaly is a heterogeneous disorder i.e. it has many different causes and a variable clinical course. Microlissencephaly is a malformation of cortical development (MCD) that occurs due to failure of neuronal migration between the third and fifth month of gestation as well as stem cell population abnormalities. Numerous genes have been found to be associated with microlissencephaly, however, the pathophysiology is still not completely understood.
The combination of lissencephaly with severe congenital microcephaly is designated as microlissencephaly only when the cortex is abnormally thick. If such combination exists with a normal cortical thickness (2.5 to 3 mm), it is known as "microcephaly with simplified gyral pattern" (MSGP). Both MLIS and MSGP have a much more severe clinical course than microcephaly alone. They are inherited in autosomal recessive manner. Prior to 2000, the term “microlissencephaly” was used to designate both MLIS and MSGP.
Causes of lissencephaly can include viral infections of the uterus or the fetus during the first trimester, or insufficient blood supply to the fetal brain early in pregnancy. There are also a number of genetic causes of lissencephaly, including mutation of the reelin gene (on chromosome 7), as well as other genes on the X chromosome and on chromosome 17. Genetic counseling is usually offered if there is a risk of lissencephaly, coupled with genetic testing.
The overall prognosis is excellent in most cases. Most children with Adams–Oliver syndrome can likely expect to have a normal life span. However, individuals with more severe scalp and cranial defects may experience complications such as hemorrhage and meningitis, leading to long-term disability.
There is no known definitive single mechanism that causes colpocephaly. However, researchers believe there are many possible causes of colpocephaly. It is a common symptom of other neurological disorders in newborns, can be caused as a result of shunt treatment of hydrocephalus, developmental disorders in premature infants, due to intrauterine disturbances during pregnancy, genetic disorders, underdevelopment or lack of white matter in the cerebrum, and exposure of the mother and the developing fetus to medications, infections, radiation, or toxic substances. Also, it is usually more common in premature infants than in full-term infants, especially in babies born with hypoxia or lung immaturity.
Some of the central nervous system disorders which are associated with colpocephaly are as follows:
- polymicrogyria
- Periventricular leukomalacia (PVL)
- intraventricular hemorrhage
- Hydrocephalus
- schizencephaly
- microgyria
- microcephaly
- Pierre-Robin syndrome
- Neurofibromatosis
Often colpocephaly occurs as a result of hydrocephalus. Hydrocephalus is the accumulation of cerebrospinal fluid (CSF) in the ventricles or in the subarachnoid space over the brain. The increased pressure due to this condition dilates occipital horns causing colpocephaly.
The most generally accepted theory is that of neuronal migration disorders occurring during the second to fifth months of fetal life. Neuronal migration disorders are caused by abnormal migration, proliferation, and organization of neurons during early brain development. During the seventh week of gestation, neurons start proliferating in the germinal matrix which is located in the subependymal layer of the walls of the lateral ventricles. During the eighth week of gestation, the neurons then start migrating from the germinal zone to cortex along specialized radial glial fibers. Next, neurons organize themselves into layers and form synaptic contacts with other neurons present in the cortex. Under normal conditions, the neurons forming a germinal layer around ventricles migrate to the surface of the brain and form the cerebral cortex and basal ganglia. If this process is abnormal or disturbed it could result in the enlargement of the occipital horns of the lateral ventricles. Common prenatal disturbances that have been shown to disturb the neuronal migration process include the following:
- continuation of oral contraceptives
- exposure to alcohol
- intrauterine malnutrition
- intrauterine infections such as toxoplasmosis
- maternal drug ingestion during early pregnancy such as corticosteroids, salbutamol, and theophylline
Researchers also believe that these factors can cause destruction of neural elements that have previously been normally formed.
It is suggested that the underdevelopment or lack of white matter in the developing fetus could be a cause of colpocephaly. The partial or complete absence of white matter, also known as agenesis of the corpus callosum results in anatomic malformations that can lead to colpocephaly. This starts to occur around the middle of the second month to the fifth month of pregnancy. The lateral ventricles are formed as large cavities of the telencephalic vesicle. The size of the ventricles are decreased in normal development after the formation of the Foramen of Magendie, which decompresses the ventricular cavities. Myelination of the ventricular walls and association fibers of the corpus callosum and the calcarine fissure helps shape the occipital horns. In cases where this developmental process is interrupted, occipital horns are disproportionately enlarged.
Colpocephaly has been associated with chromosomal abnormalities such as trisomy 8 mosaic and trisomy 9 mosaic. A few reports of genetically transmitted colpocephaly are also found in literature. Some of these are of two siblings, monozygotic twins, and non-identical twins. The authors suggest a genetic origin with an autosomal or X-linked recessive inheritance rather than resulting from early prenatal disturbances.
Many of the congenital malformations found with Malpuech syndrome can be corrected surgically. These include cleft lip and palate, omphalocele, urogenital and craniofacial abnormalities, skeletal deformities such as a caudal appendage or scoliosis, and hernias of the umbillicus. The primary area of concern for these procedures applied to a neonate with congenital disorders including Malpuech syndrome regards the logistics of anesthesia. Methods like tracheal intubation for management of the airway during general anesthesia can be hampered by the even smaller, or maldeveloped mouth of the infant. For regional anesthesia, methods like spinal blocking are more difficult where scoliosis is present. In a 2010 report by Kiernan et al., a four-year-old girl with Malpuech syndrome was being prepared for an unrelated tonsillectomy and adenoidectomy. While undergoing intubation, insertion of a laryngoscope, needed to identify the airway for the placement of the endotracheal tube, was made troublesome by the presence of micrognathia attributed to the syndrome. After replacement with a laryngoscope of adjusted size, intubation proceeded normally. Successful general anesthesia followed.
A rare follow-up of a male with Malpuech syndrome was presented by Priolo et al. (2007). Born at term from an uneventful pregnancy and delivery, the infant underwent a surgical repair of a cleft lip and palate. No problems were reported with the procedure. A heart abnormality, atrial septal defect, was also apparent but required no intervention. At age three years, mental retardation, hyperactivity and obsessive compulsive disorder were diagnosed; hearing impairment was diagnosed at age six, managed with the use of hearing aids. Over the course of the decade that followed, a number of psychiatric evaluations were performed. At age 14, he exhibited a fear of physical contact; at age 15, he experienced a severe psychotic episode, characterized by agitation and a loss of sociosexual inhibition. This array of symptoms were treated pharmocologically (with prescription medications). He maintained a low level of mental deficiency by age 17, with moments of compulsive echolalia.
Trisomy 22 is a chromosomal disorder in which there are three copies of chromosome 22 rather than two. It is a frequent cause of spontaneous abortion during the first trimester of pregnancy. Progression to the second trimester and live birth are rare. This disorder is found in individuals with an extra copy or a variation of chromosome 22 in some or all cells of their body. There are many kinds of disorders associated with Trisomy 22:
Emanuel Syndrome is named after the genetic contributions made by researcher Dr. Beverly Emanuel. This condition is assigned to individuals born with an unbalanced 11/22 translocation. That is, a fragment of chromosome 11 is moved, or translocated, to chromosome 22.
22q11 Deletion Syndrome is a rare condition which occurs in approximately 1 in 4000 births. This condition is identified when a band in the q11.2 section of the arm of chromosome 22 is missing or deleted. This condition has several different names: 22q11.2 Deletion Syndrome, Velocardiofacial syndrome, DiGeorge Syndrome, Conotruncal Anomaly Face syndrome, Opitz G/BBB Syndrome, and Cayler Cardiofacial Syndrome. The effects of this disorder are different in each individual but similarities exist such as heart defects, immune system problems, a distinctive facial appearance, learning challenges, cleft palate, hearing loss, kidney problems, hypocalcemia, and sometimes psychiatric issues.
22q11 microduplication syndrome is the opposite of the 22q11 deletion syndrome: in this condition, a band of q.11.2 section of chromosome 22 is duplicated. Individuals carrying this deficiency are relatively “normal” as in they don’t possess any major birth defects or major medical illnesses. This microduplication is more common than the deletion; this might be due to the milder phenotype of the individuals.
Phelan-McDermid Syndrome / 22q13 Deletion Syndrome is a condition caused by the deletion of the tip of the q arm on chromosome 22. Most individuals with this disorder experience cognitive delays; low muscle tone; and sleeping, eating, and behavioural issues.
Chromosome Ring 22 is a rare disorder caused by the break and re-join of both ends of chromosome 22, forming a ring. The effects on the individual with this disorder are dependent on the amount of genetic information lost during the break/re-join. Major characteristics for this disorder are intellectual disability, muscle weakness and lack of coordination.
Cat Eye Syndrome / Schmid Fraccaro Syndrome is a condition caused by a partial trisomy or tetrasomy in chromosome 22. A small extra chromosome is found, made up of the top half of chromosome 22 and a portion of the q arm at the q11.2 break. This chromosome can be found three or four times. This syndrome is referred as “Cat Eye” due to the eye appearance of reported affected individuals who have coloboma of the iris; however, this feature is only seen in about half of the cases.
Mosaic trisomy 22 is a disorder in which an extra chromosome 22 is found only in some cells of the body. The severity of each case is determined by the number of cells with this extra copy. Some characteristics of individuals with this condition are cardiac abnormalities, growth retardation, mental delay, etc.
Complete Trisomy 22 is in contrast with Mosaic trisomy 22; this disorder is characterized by an extra copy of chromosome 22 which is found in each cell of the body of the affected individual. These cases are very rare, and most of the affected individuals die before birth or shortly after.
Malpuech syndrome has been shown to have physical, or phenotypical similarities with several other genetic disorders. A report by Reardon et al. (2001) of a nine-year-old boy exhibiting facial, caudal and urogenital anomalies consistent with Malpuech syndrome, who also had skeletal malformites indicative of Juberg-Hayward syndrome, suggests that the two disorders may be allelic (caused by different mutations of the same gene).
Along with several other disorders that have similar, or overlapping features and autosomal recessive inheritance, Malpuech syndrome has been considered to belong under the designation "3MC syndrome". Titomanlio et al. (2005) described a three-year-old female known to have Michels syndrome. In their review of the physical similarities between Michels, Malpuech and Mingarelli-Carnevale syndromes—particularly the facial appearance including instances of cleft lip and palate, and ptosis, and a similarity of congenital abdominal and urogenital anomalies—they believed the syndromes may represent a spectrum of genetic disorders rather than three individual disorders. They initially suggested this spectrum could be named 3MC (Michels-Malpuech-Mingarelli-Carnevale) syndrome. This conclusion and the name 3MC syndrome was supported by Leal et al. (2008), who reported a brother and sister with an array of symptoms that overlapped the various syndromes. Further assertion of 3MC syndrome was by Rooryck et al. (2011) in an elaboration of its cause.
The prognosis for children with NMDs varies depending on the specific disorder and the degree of brain abnormality and subsequent neurological signs and symptoms.
In a newborn boy thought to have Fryns syndrome, Clark and Fenner-Gonzales (1989) found mosaicism for a tandem duplication of 1q24-q31.2. They suggested that the gene for this disorder is located in that region. However, de Jong et al. (1989), Krassikoff and Sekhon (1990), and Dean et al. (1991) found possible Fryns syndrome associated with anomalies of chromosome 15, chromosome 6, chromosome 8(human)and chromosome 22, respectively. Thus, these cases may all represent mimics of the mendelian syndrome and have no significance as to the location of the gene for the recessive disorder.
By array CGH, Slavotinek et al. (2005) screened patients with DIH and additional phenotypic anomalies consistent with Fryns syndrome for cryptic chromosomal aberrations. They identified submicroscopic chromosome deletions in 3 probands who had previously been diagnosed with Fryns syndrome and had normal karyotyping with G-banded chromosome analysis. Two female infants were found to have microdeletions involving 15q26.2 (see 142340), and 1 male infant had a deletion in band 8p23.1 (see 222400).
In general, gray matter heterotopia is fixed in both its occurrence and symptoms; that is, once symptoms occur, it does not tend to progress. Varying results from surgical resection of the affected area have been reported. Although such surgery cannot reverse developmental disabilities, it may provide full or partial relief from seizures.
Heterotopia are most commonly isolated anomalies, but may be part of a number of syndromes, including chromosomal abnormalities and fetal exposure to toxins (including alcohol).
Microcephalic osteodysplastic primordial dwarfism (MOPD) type II is an autosomal multisystem disorder including severe pre- and post-natal growth retardation, microcephaly with Seckel syndrome-like facial appearance, and distinctive skeletal alterations. Usually those affected have mild to moderate mental retardation. This female child is the first born of nonconsanguineous parents at 35 weeks gestation through a cesarean section due to intrauterine growth retardation. She had a retarded psychomotor development and was repeatedly hospitalized during her first six months of life due to recurring respiratory infections. Her electroencephalography, auditory brainstem response evaluation, and chromosomal analysis were relatively normal. A brain MRI revealed thickened cerebral cortices with few and large gyri prominently in the frontal and posterior temporal regions, incomplete development of the Sylvian fissures, and dilatation of the posterior horns of the lateral ventricles (colpocephaly). Usually only mild brain malformations are associated with MOPD type II. The imaging findings of this child’s brain most likely represent diffuse pachygyria, a mild form of lissencephaly. This child’s neurodevelopmental findings were mild when compared to previous reports of a well-defined chromosome 17-linked and X-linked lissencephaly in a bedridden patient with severe developmental delays.
AOS is a rare genetic disorder and the annual incidence or overall prevalence of AOS is unknown. Approximately 100 individuals with this disorder have been reported in the medical literature.
Neu–Laxova syndrome (also known as Neu syndrome or Neu-Povysilová syndrome, abbreviated as NLS) is a rare autosomal recessive disorder characterized by severe intrauterine growth restriction and multiple congenital malformations. Neu–Laxova syndrome is a very severe disorder, leading to stillbirth or neonatal death. It was first described by Dr. Richard Neu in 1971 and Dr. Renata Laxova in 1972 as a lethal disorder in siblings with multiple malformations. Neu–Laxova syndrome is an extremely rare disorder with less than 100 cases reported in medical literature.
West syndrome appears in 1% to 5% of infants with Down syndrome. This form of epilepsy is relatively difficult to treat in children who do not have the chromosomal abnormalities involved in Down syndrome. However, in children with Down syndrome, the syndrome is often far more mild, and the children often react better to medication. The German Down Syndrom InfoCenter noted in 2003 that what was normally a serious epilepsy was in such cases often a relatively benign one.
EEG records for children with Down syndrome are often more symmetrical with fewer unusual findings. Although not all children can become entirely free from attacks with medication, children with Down syndrome are less likely to go on to develop Lennox-Gastaut syndrome or other forms of epilepsy than those without additional hereditary material on the 21st chromosome. The reason why it is easier to treat children with Down syndrome is not known.
If, however, a child with Down syndrome has seizures that are difficult to control, the child should be accessed for autistic spectrum disorder.
Colpocephaly is usually non-fatal. There has been relatively little research conducted to improve treatments for colpocephaly, and there is no known definitive treatment of colpocephaly yet. Specific treatment depends on associated symptoms and the degree of dysfunction. Anticonvulsant medications can be given to prevent seizure complications, and physical therapy is used to prevent contractures (shrinkage or shortening of muscles) in patients that have limited mobility. Patients can also undergo surgeries for stiff joints to improve motor function. The prognosis for individuals with colpocephaly depends on the severity of the associated conditions and the degree of abnormal brain development.
A rare case of colpocephaly is described in literature which is associated with macrocephaly instead of microcephaly. Increased intracranial pressure was also found in the condition. Similar symptoms (absence of corpus callosum and increased head circumference) were noted as in the case of colpocephaly that is associated with microcephaly. A bi-ventricular peritoneal shunt was performed, which greatly improved the symptoms of the condition. Ventriculo-peritoneal shunts are used to drain the fluid into the peritoneal cavity.
The varied signs and symptoms of Duane-radial ray syndrome often overlap with features of other disorders.
- For example, acro-renal-ocular syndrome is characterized by Duane anomaly and other eye abnormalities, radial ray malformations, and kidney defects. Both conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Duane-radial ray syndrome and acro-renal-ocular syndrome are separate disorders or part of a single syndrome with many possible signs and symptoms.
- The features of Duane-radial ray syndrome also overlap with those of a condition called Holt-Oram syndrome; however, these two disorders are caused by mutations in different genes.