Lissencephaly

Question 1

Lissencephaly

Answer 1

• “Smooth brain”
• Genetic malformation of the cerebral cortex in which abnormal neuronal migration in early development results in smooth cerebral surfaces with absent (agyria) or decreased (pachygyria) convolutions.
• In children, characterized by seizures, cognitive dysfunction, poor feeding, and spasticity

Question 2

Miller-Dieker syndrome

Answer 2

• Inherited form of lissencephalopathy
• Due to a microdeletion on chromosme 17
  
  • 80% de novo, 20% inherited
• Agyria and dysmorphic features

Question 3

Isolated lissencephaly sequence

Answer 3

• Milder phenotype of lissencephaly compared to Miller-Dieker syndrome
• Pachygryria, mild or absent dysmorphic features
• LIS1 form: AD on chr17. Pachygyria is primarily posterior
• Doublecortin form: X-linked. Pachygyria is primarily anterior

Question 4

Subcortical band heterotropia

Answer 4

• A radiographic finding
• Band of heterotropic gray matter located just beneath the cortex and separated by a thin wall of normal white matter

Question 5

Infantile spasms

Answer 5

• Dramatic, repetitive bouts of rapid neck flexion, arm extension, hip and knee flexio, etc, often with arousal from sleep
• Parents may describe them as unprovoked startle responses or colicky spells due to abdominal pain, but without crying
• Typical presentation between 3-8 months of age

Question 6

Hypertelorism

Answer 6

Abnormally increased distance between the eyes

Question 7

Epicanthal fold

Answer 7

Skin fold of the upper eyelid covering the medial corner of the eye

Question 8

Clinodactyly

Answer 8

• Congenital condition where the little finger is curved towards the ring finger

Question 9

Treament for lissencephaly

Answer 9

• ACTH or prednisone to prevent infantile spasms (used with varying success)
• Feeding tube and gastrostomy to prevent aspiration long-term (aspiration and pneumonia are a common cause of death)
• Physical therapy and muscle relaxants to slow the development of spasms and contractures, which may cause falls, atelectasis, decubitus ulcers
• Treatment of congenital heart and kidney anomalies

Question 10

Genetic counseling in lissencephalopathy

Answer 10

Recurrence risk is very low for most cases, as most mutations are de novo.

However, if a recpirocal translocation is identified, recurrence risk can be as high as 33%

Question 11

Diagnosis of lissencephaly

Answer 11

• In utero:
  
  • Karyotyping, FISH, amniocentesis, chorionic villus sampling
  • Imaging for cerebral gyral malformations (if beyond 28 weeks)
• In a child:
  
  • Neuroimaging
  • FISH

Question 12

Clinical hallmarks of Miller-Dieker syndrome

Answer 12

• Microcephaly with abnormal fascies
• Motor delay (with spasms)
• Cognitive delay
• Seizures

Question 13

__ can mimic infantile spasms, but will always occur after a child eats, and the child will typically be developmentally normal

Answer 13

Intestinal colic can mimic infantile spasms, but will always occur after a child eats, and the child will typically be developmentally normal

This might make you suspect intussusception