A Rare Case of Microcephaly-Capillary Malformation Syndrome Diagnosed via Whole Exome Sequencing (P6.018)

Objective: To describe the role of Whole Exome Sequencing in diagnosing a rare case of Microcephaly-Capillary Malformation (MIC-CAP) Syndrome. Background: MIC-CAP Syndrome is a rare autosomal recessive syndrome characterized by profound microcephaly, cutaneous capillary malformations, severe developmental delay and intractable epilepsy. To date, there have been approximately 12 cases described world-wide. In this abstract, we describe the role of whole exome sequencing in uncovering this rare neurogenetic syndrome. Design/Methods: Clinical data were extracted via detailed chart review. Whole exome sequencing was performed and independently verified at two institutions. Results: The proband, a 2 day old male infant was born at 39 weeks. Prenatal care was unremarkable. Apgars were 9 and 9 at 1 and 5 minutes, respectively. He was noted to have several macules on his body. At 24 hours of life, he developed clinical and subclinical seizures, refractory to anti-epileptic drugs. Testing was ultimately carried out at the Children’s Hospital of Eastern Ontario Research Institute, Inc. Simultaneously, whole genome sequencing was initiated at the Baylor College of Medicine. At age 5 months, results were received from the research laboratory confirming 2 mutations in the STAMBP gene. The first mutation c299T>A results in a p.Phe100Tyr occurs at a highly conserved amino acid position and has been reported before by the lab as a mutation in another affected individual. The second mutation is a c.753_754insT and creates a nonsense mutation. These findings were verified by whole exome sequencing at Baylor College of Medicine. Both parents were confirmed as carriers. Discussion: Whole exome sequencing (WES) was successful in identifying 2 mutations known to result in MIC-CAP Syndrome, a rare neurogenetic syndrome characterized by severe microcephaly, developmental delay, intractable epilepsy, and cutaneous hemangiomas. WES appears to be a promising tool for identifying rare neurogenetic syndromes for which more targeted sequencing is unavailable. Though the process is lengthy (15 weeks), WES offers families and providers a valuable tool in diagnosing rare neurogenetic syndromes.

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