Miller–Dieker syndrome (lissencephaly)
A deletion on chromosome 17 that stops neurons from migrating in the fetal brain, leaving a smooth brain, severe disability and epilepsy.
What it is
A contiguous-gene deletion at 17p13.3 that includes PAFAH1B1 (LIS1) and YWHAE, causing classic lissencephaly with distinctive facial features.
Who gets it
Rare: about 1 in 100 000 births.
Causes
- Heterozygous deletion of 17p13.3 including PAFAH1B1 and YWHAE
- Usually de novo; sometimes from a parent's balanced translocation, which raises the recurrence risk
Pathophysiology
LIS1 is needed for the movement of neurons from where they are born, near the ventricles, out to the cortex. With one copy lost, migration fails: the cortex is thick and disorganised and the surface lacks normal folds (smooth brain). Loss of YWHAE as well makes the brain and facial findings more severe than in isolated LIS1 lissencephaly.
Classification
- Miller–Dieker syndrome: larger deletion (LIS1 plus YWHAE) with facial features
- Isolated lissencephaly sequence: smaller LIS1 deletion or variant, without the facial features
Symptoms and signs
- Severe intellectual disability and developmental delay
- Epilepsy, often infantile spasms, beginning in the first months
- Feeding difficulty and failure to thrive
- Early low muscle tone, later stiffness
- Small head and distinctive face (prominent forehead, short nose, thick upper lip)
Diagnosis
- Clinical
- Suspected in an infant with severe delay, seizures and a typical face; brain imaging shows lissencephaly.
- Tests
- Chromosomal microarray or FISH for 17p13.3; parental testing to look for a balanced translocation.
- Imaging
- Brain MRI shows a smooth brain surface with a thick cortex; fetal MRI may suggest it late in pregnancy.
Treatment
- Medical
- Antiseizure treatment, often difficult.
- Surgical
- Gastrostomy for feeding and aspiration risk.
- Rehabilitation
- Physical therapy and supportive care.
- Follow-up
- Monitoring for respiratory infections and nutrition.
Complications
- Refractory epilepsy
- Aspiration pneumonia
- Early death in many children
Prognosis
Severe; many children die in childhood, mostly from aspiration or seizures.
Test yourself
Think of the answer, then tap the question to see it.
What does LIS1 do in brain development?
It is needed for neurons to migrate from the ventricular zone to the cortex.
Why should parents of a child with Miller–Dieker syndrome be tested?
One may carry a balanced translocation, which greatly raises the recurrence risk.
How does Miller–Dieker syndrome differ from isolated lissencephaly sequence?
Its larger deletion also removes YWHAE, giving more severe brain findings and the characteristic face.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Miller-Dieker syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Isolated lissencephaly sequence: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); PAFAH1B1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.