What is Miller-Dieker Lissencephaly syndrome (MDLS)?
Miller-Dieker Lissencephaly is a rare genetic syndrome. The main condition of the syndrome is lissencephaly, abnormal brain development that leads to the development of a brain without the normal folds and grooves. Instead, the brain is smooth. This, in turn, causes many of the main symptoms of the syndrome. The severity of the syndrome depends on how smooth the brain is.
This syndrome is also known as:
Lissencephaly syndrome MDLS; Chromosome 17p13.3 deletion syndrome
What gene changes cause Miller-Dieker Lissencephaly syndrome (MDLS)?
The syndrome is caused by a deletion of genetic material on or near the short arm of chromosome 17p13.3. The size of this deletion varies between individuals, and the size of the deletion may explain why some affected individuals have more severe symptoms than others.
The syndrome can be inherited in an autosomal dominant pattern but most cases are the result of de novo or new deletions that occur during reproduction.
In the case of autosomal dominant inheritance, just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.
In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation which occurs during the reproductive process.
However, syndromes with similar characteristics are associated with changes in upto 16 differents genes, which should be considered as differential diagnoses.
What are the main symptoms of Miller-Dieker Lissencephaly syndrome (MDLS)?
Lissencephaly is the main symptom of the syndrome. That affects the cerebral cortex of the exterior surface of the brain. The abnormal development caused by the syndrome leads to a brain with less folds and grooves than usual and a smoother brain as a result.
This abnormal brain development triggers further symptoms. These include severe intellectual disability and developmental delay. Seizures, muscle stiffness, low muscle tone, and feeding issues are amongst these symptoms.
Unique facial features of the syndrome include a prominent forehead, a sunken middle of the face, a small nose, a low set and abnormally shaped ears, a small jaw, and a thick upper lip. In some individuals, slower growth is recorded.
Possible clinical traits/features:
Abnormality of metabolism/homeostasis, Abnormality of the cardiovascular system, Cavum septum pellucidum, Cataract, Wide nasal bridge, Cerebral cortical atrophy, Polyhydramnios, Cleft palate, Aplasia/Hypoplasia of the corpus callosum, Short nose, Anteverted nares, Nephropathy, Lissencephaly, Low-set ears, Midline brain calcifications, Micrognathia, Intellectual disability, Intrauterine growth retardation, Inguinal hernia, Infantile muscular hypotonia, Joint contracture of the hand, High forehead, Gray matter heterotopia, Hypoplasia of the corpus callosum, Incoordination, Failure to thrive, Delayed eruption of teeth, Motor delay, Deep palmar crease, Duodenal atresia, Epicanthus, EEG abnormality, Decreased fetal movement, Cryptorchidism, Clinodactyly of the 5th finger, Malformation of the heart and great vessels, Contiguous gene syndrome, Thick upper lip vermilion, Thin upper lip vermilion, Microcephaly, Infantile spasms, Recurrent aspiration pneumonia, Camptodactyly, Progressive spastic paraplegia.
How is it diagnosed?
To find out if someone has a diagnosis of Miller-Dieker Lissencephaly syndrome (MDLS), it is important to have a consultation and evaluation with a clinical genetic specialist. Specialists may also suggest specific genetic testing or other types of tests to help reach a diagnosis. FDNA’s AI technology can help speed up the diagnostic process by analyzing facial features and other health information.
