Miller-Dieker syndrome is a rare disorder with contiguous gene deletion that is characterized by lissencephaly, distinct facial and other congenital anomalies. It is associated with seizures, mental delay, and early death.
Miller-Dieker syndrome (MDS), is a disorder with abnormal neuronal migration during brain development due to an underlying deletion at chromosome 17p13.3 . This rare disease features classic lissencephaly (smooth brain), which is characterized by agyria (absence of brain convolutions) or frontal pachygyria (few brain convolutions) . MDS also consists of microcephaly and profound facial dysmorphisms such as a prominent forehead, bitemporal hollowing, down-slanting palpebral fissures, short nose accompanied by upturned nares, protuberant upper lip, downturned vermillion border, and micrognathia  . Occasionally, other anomalies like congenital heart malformations, genitourinary defects, and omphalocele may also be present  .
MDS is associated with a very poor prognosis. Affected children have severe developmental retardation and are at risk of dying within a few years of life  . Complications include severe neurologic and mental delay, epilepsy, growth restriction, as well as trouble with feeding  .
Entire Body System
- Upturned Nares
All had severe type I lissencephaly with grossly normal cerebellum and a distinctive facial appearance consisting of prominent forehead, bitemporal hollowing, short nose with upturned nares, protuberant upper lip, thin vermilion border, and small jaw. [ncbi.nlm.nih.gov]
However, hypotonia and abnormal facial morphology including prominent forehead, a short nose with upturned nares and protuberant upper lip were developed gradually as he got older. [synapse.koreamed.org]
Miller-Dieker syndrome: A congenital malformation syndrome characterized by lissencephaly ("smooth brain") and a characteristic facial appearance with a prominent forehead with bitemporal hollowing, short nose with upturned nares, thickened upper lip [medicinenet.com]
On examination, child had microcephaly, prominent forehead, a wide nasal bridge, low-set ears, upturned nares, long philtrum (vertical groove on the midline of the upper lip) with thin upper lip, mild micrognathia and delayed dentition [Figure 1]. [ssajm.org]
An infant with the clinical presentation discussed above or a fetus with suspicious findings observed on prenatal ultrasonography warrants a full workup that consists of patient/fetal and family history, a detailed physical exam of the infant, and the appropriate studies discussed below.
Obstetric ultrasonography can detect MDS prenatally if performed during late second trimester or later by an experienced operator . Ultrasound scans on fetuses with this disease reveal findings such as a smooth gyral pattern consistent with lissencephaly, ventriculomegaly, other brain abnormalities, intrauterine growth restriction (IUGR), and polyhydramnios  . Additionally, congenital anomalies such as omphalocele and heart defects are also identified prenatally .
Amniocentesis or chorionic villus sampling (CVS) and subsequent cytogenic analysis can confirm the diagnosis in a fetus suspected to have MDS.
A study reviewing brain computerized tomography (CT) scans and magnetic resonance imaging (MRI) of affected infants demonstrate features such as smooth cerebral hemispheres and a remarkable figure of eight appearance . Frequent findings include a thickened cortex, enlarged cavum septi pellucidi, and diminished or absent corpus callosum . Furthermore, enlarged ventricles and midline calcifications may also be observed . Another study also reported lissencephaly and agenesis of the corpus callosum on CT imaging .
Patients suspected to have MDS should undergo chromosomal analysis with fluorescence in situ hybridization (FISH) in order to confirm the deletion of the 17p13.3 locus. MDS is associated with multiple genes including LIS1, YWHAE, and CRK in addition to contiguous genes that would contribute to the manifestations of severe forms of the disease  .
Distinct electroencephalogram (EEG) results associated with MDS include abnormally high amplitude,and rhythmic slow activities .
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