Miller-Dieker syndrome
Encyclopedia
Miller–Dieker syndrome also called Miller–Dieker lissencephaly syndrome (MDLS) and chromosome 17p13.3 deletion syndrome, is an autosomal
dominant congenital disorder
characterized by a developmental defect of the brain
, caused by incomplete neuronal migration.
This syndrome should not be confused with Miller syndrome
- an unrelated rare genetic disorder - or Miller Fisher syndrome - a form of Guillain-Barré syndrome
.
is smooth (also known as lissencephaly
), has an absence of sulci
and gyri
, has a cerebral cortex
4 layers thick instead of 6 and shows microcephaly
. There is a characteristic facial appearance, delayed growth and mental development, and multiple abnormalities of the brain
, heart
, kidney
and gastrointestinal tract
.
Failure to thrive
, feeding difficulties, seizure
s and decreased spontaneous activity are often seen, and death
tends to occur in infancy and childhood.
Cause and Genetic has an autosomal dominant pattern of inheritance
.]]
Originally thought to be an
The disorder arises from the deletion
of part of 17p (which includes both the LIS1 and 14-3-3 epsilon gene), leading to partial monosomy
. There may be unbalanced translocations
(ie 17q:17p or 12q:17p), or the presence of a ring chromosome
17.
Although an autosomal dominant disorder, Miller-Dieker syndrome is not easily inherited due to the fact that those afflicted do not always live beyond childho050093}} They therefore could not pass the gene to the next generation.
Diagnosis
External links
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
dominant congenital disorder
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
characterized by a developmental defect of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, caused by incomplete neuronal migration.
This syndrome should not be confused with Miller syndrome
Miller syndrome
This condition is also known as the Genee-Wiedemann syndrome, Wildervanck-Smith syndrome or postaxial acrofacial dystosis . The incidence of this condition is not known but it is considered extremely rare...
- an unrelated rare genetic disorder - or Miller Fisher syndrome - a form of Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
.
Characteristics
The brainBrain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
is smooth (also known as lissencephaly
Lissencephaly
Lissencephaly, which literally means smooth brain, is a rare brain formation disorder caused by defective neuronal migration during the 12th to 24th weeks of gestation, resulting in a lack of development of brain folds and grooves . It is a form of cephalic disorder...
), has an absence of sulci
Sulcus (neuroanatomy)
In neuroanatomy, a sulcus is a depression or fissure in the surface of the brain.It surrounds the gyri, creating the characteristic appearance of the brain in humans and other large mammals....
and gyri
Gyrus
A gyrus is a ridge on the cerebral cortex. It is generally surrounded by one or more sulci .-Notable gyri:* Superior frontal gyrus, lat. gyrus frontalis superior* Middle frontal gyrus, lat. gyrus frontalis medius...
, has a cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
4 layers thick instead of 6 and shows microcephaly
Microcephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
. There is a characteristic facial appearance, delayed growth and mental development, and multiple abnormalities of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
and gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
.
Failure to thrive
Failure to thrive
Failure to thrive is a medical term which is used in both pediatric and adult human medicine, as well as veterinary medicine ....
, feeding difficulties, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s and decreased spontaneous activity are often seen, and death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
tends to occur in infancy and childhood.
Cause and Genetic has an autosomal dominant pattern of inheritance
Heredity
Heredity is the passing of traits to offspring . This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve...
.]]
Originally thought to be an
The disorder arises from the deletion
Deletion
Deletion is the act of deleting or removal by striking out material, such as a word or passage, that has been removed from a body of written or printed matter.Deletion may refer to:*File deletion, a way of removing a file from a computer's file system...
of part of 17p (which includes both the LIS1 and 14-3-3 epsilon gene), leading to partial monosomy
Monosomy
Monosomy is a form of aneuploidy with the presence of only one chromosome from a pair. Partial monosomy occurs when only a portion of the chromosome has one copy, while the rest has two copies.-Human monosomy:...
. There may be unbalanced translocations
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
(ie 17q:17p or 12q:17p), or the presence of a ring chromosome
Ring chromosome
A ring chromosome is a chromosome whose arms have fused together to form a ring. A ring chromosome is denoted by the symbol r. Ring chromosomes may form in cells following genetic damage by mutagens like radiation, they may also arise spontaneously during development.-Formation:Normally, the ends...
17.
Although an autosomal dominant disorder, Miller-Dieker syndrome is not easily inherited due to the fact that those afflicted do not always live beyond childho050093}} They therefore could not pass the gene to the next generation.
Diagnosis