Miller-Dieker Syndrome (MDS)

#OMIM Reference: 
Gene (#OMIM): 
PAFAH1B1 / LIS1 (*601545)

Miller-Dieker syndrome (MDS) is caused by a contiguous gene deletion. Classical LIS is accompanied by distinct dysmorphic facial features, including prominent forehead, bitemporal hollowing, flattened ear helices, mild hypertelorism, epicanthic folds, short nose and anteverted nares, prominent lateral nasal folds and round philtrum. Additional malformations can be observed including cardiac and structural renal anomalies. Children with MDS present with severe developmental delay. Generalised hypotonia is a prominent feature early in life, with increasing spasticity as the patients get older. Epilepsy is present, often as infantile spasms, in almost cases. Feeding and swallowing problems are common, and can be complicated by aspiration pneumonia. The head circumference is small to normal at birth, but older patients are usually microcephalic. Additional features include cardiac and structural renal anomalies.
Affected children have severe delay, epilepsy and feeding problems.

 Deletions of 17p13.3, including the LIS1 gene, are found in almost 100% of patients. Deletion of two additional genes, CRK and 14-3-3e, telomeric to LIS1, may contribute to the most severe LIS grade and dysmorphic features observed in MDS. In about 12% of patients the deletion is the result of a familial chromosomal rearrangement.
    The recurrence risk for MDS is very low, as the chromosomal deletion is usually a de novo event. However if it is associated with a familial reciprocal translocation, the recurrence risk for an abnormal live born can be as high as 33%. There appears to be a higher incidence of monosomy 17p and MDS than trisomy 17p, which has a milder phenotype.

We have used a new diagnostic method to characterize small genomic deletions/duplications involving the LIS1 gene in patients with isolated LIS that were resulted negative to FISH analysis. This method can also be used for identifying contiguous gene deletions in MDS patients.

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