Smooth brain : A case of Miller Dieker syndrome. 


Dr.Akshay Kishore , Dr.Vinitha Prasad , Dr.Vinayan KP , Dr.C.Jayakumar , Amrita institute of medical sciences. 

Five month old child Term with vital perinatal history presented with complaints of sudden onset spasm occurring as clusters during awake state for 2 days duration. 
Semiology being flexion of neck and upper limbs lasting for 10 seconds like salaam spells. Eight to ten episodes used to occur per day.
Child has not attained neck holding 5.5 months of age and there was no unidextrous reach also. 
Differential diagnosis considered were 
1.Infantile spasm – West syndrome 
2.Structural abnormalities of the brain 
3.Inborn errors of metabolism 
4.Intra uterine infections 
5.Chromosomal anomalies 

On examination child has dysmorphism – low set ears , flat nasal bridge , bitemporal hollowing and retrognathia. Vitals were stable
Auxology – Length 60cm (-2SD and -3SD) 
Weight – 5kg (-1 and -2SD) 
HC – 39cm(<3SD)
There was microcephaly (39cm). 
There was no neuro cutaneous markers. 
Anterior fontanelle was at level. 
CNS examination revealed generalised hypertonia with brisk reflexes. Ba was not following light. 
There was no signs of meningeal irritation , nystagmus or ptosis. There was no fasciculation or generalized wasting. 
Labs done showed negative for sepsis screen. 
LFT/RFT/S.Electrolytes were normal. 
Ammonia and lactate was normal. 
EEG done showed hypsarrythmia which was suggestive of West syndrome. MRI brain done showed lissencephaly with subcortical band heterotropia. 
ECHO – small Atrial septal defect left to right. 
In view of structural abnormality of the brain and infantile spasm – 


Whole exome sequencing was sent which showed Miller Dieker syndrome. In view of west syndrome child received Inj. ACTH and was discharged on Valproate and other multidisciplinary measures. 

Discussion : Miller Dieker syndrome – very rare syndrome – 1 in 100,000 babies – Lissencephaly / subcortical band heterotopia (SBH) comprises a spectrum of severity which affects the newborns typically have mild-to-moderate hypotonia, feeding difficulties, and poor head control. During the first years, neurologic examination typically demonstrates poor visual tracking and response to sounds, mild distal spasticity that can transition over time to more severe spasticity. Clinical features include microcephaly, wrinkled skin over the glabella and frontal suture, prominent occiput, narrow forehead, downward slanting palpebral fissures, small nose and chin, cardiac malformations, hypoplastic male extrenal genitalia, growth retardation, and mental deficiency with seizures and EEG abnormalities. Facial dysmorphism and other anomalies in Miller-Dieker patients appear to be the consequence of deletion of additional genes distal to LIS1 gene. It results from a deletion in chromosome 17p13.3, which includes the PAFAH1B1 and YWHAE genes. Most of the children do not survive beyond childhood. 

Take home message : In a child with developmental delay , west syndrome , cardiac findings, always think of Miller Dieker syndrome.