A Rare Case of Microcephaly-Capillary Malformation Syndrome Diagnosed via Whole Exome Sequencing (P6.018)
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".