Presentations

Abstract

Introduction:

This case discusses a pediatric patient with Turner Syndrome, Craniosynostosis, and 1p36 deletion syndrome. The incidence of Turner Syndrome and Craniosynostosis is similar with ~1 in every 2,000 live births. In contrast, 1p36 deletion syndrome is more uncommon, occurring ~1 in every 5,000-10,000 live births (Jordan, 2015). Individually these three conditions are rare but craniosynostosis is an atypical finding in conjunction with these two disorders. The patient's sagittal subtype of Craniosynostosis is typically due to deletions on the ERF, TCF12, and MMP23B genes on chromosomes 19, 15, and 1, respectively (Jordan, 2015). However, these deletions were not present. Therefore, in the setting of 1p36 syndrome and the mutations on chromosome 1, we hoped to find lesser known mutations that caused the patient's craniosynostosis. When looking at the specific genetic mutations, we found the PIK3CD gene which was mutated due to her 1p36 syndrome. The PIK3CD gene has a known connection to, and could be a proposed cause, of her craniosynostosis. Our objectives were to discover whether there was a causative correlation between her 1p36 syndrome and the presence of craniosynostosis and if existing, solidify any connection between the patient's 1p36 syndrome, subsequent PIK3CD gene deletion, and her craniosynostosis.

Case:

A 7-year-old female with a history of turner syndrome, sagittal synostosis, and 1p36 deletion syndrome presented to the Craniofacial Clinic for a follow up post craniofacial reconstruction.

Prenatal care started at 25 weeks and the patient was born at 37 ½ weeks gestation with a complication of meconium ingestion. At birth, the patient's weight was 2775g (25th%), length 49cm (50th%), and head circumference 32cm (10th%) with microcephaly and thrombocytopenia present.

The patient's genetic analysis showed classic Turner Syndrome and a derivative chromosome 1 short arm with duplication and deletion, resulting in 1p36 microdeletion syndrome. The patient's karyotype was [45, X, der (1) dup (1) (p36.33p36.32) del (1) (p36.32p36.22)]. Her CMA report for chromosome 1 was [arr (X) x1, 1p36.33p36.32 (1,474167-4,294,000) x3, 1p36.32p36.22 (5,150,534-10,936,544) x1].

The patient underwent a bifrontal craniotomy, vertex craniectomy and osteotomy x 10 at 17 months. The plan was to complete Craniofacial reconstruction for correction of sagittal craniosynostosis to include a complete cranial vault remodeling, cranioplasties with cranial bone grafts to the frontal, temporal and parietal areas, and elevation of rotational bilateral temporalis muscles.

Pre-operatively, the patient's head circumference was 44.5cm, cranial index was 75.6%, with increased anteroposterior dimension and narrowed bitemporal dimension of the head. Right cranial length was 14.3cm and the left cranial length was 15.20cm.

Post-operatively seven years later, the patient's head circumference was 48.5cm, cranial index was 90%, measured Lateral Head width of 13.5cm, Anterior Posterior Length of 15cm, Right Oblique length of 14.8cm, Left Oblique Length of 15cm. No deformities were detected.

Discussion:

To identify the presence of a causative correlation between a mutation in the PIK3CD gene and the presence of craniosynostosis, we gathered data from the genetic report of this patient with all three syndromes. We submitted the genes from the patient's deletion sequence into the Franklin database to determine which genes had known clinical associations. We then characterized the effect of each gene and isolated the ones typically affected in Turner Syndrome and 1p36 deletion syndrome separately. We then cross-referenced the genes between the three groups: the patient, genes involved in Turner Syndrome, and genes involved in 1p36 deletion to determine what genes were common among the groups and identify if craniosynostosis could be attributed to Turner Syndrome, 1p36 deletion syndrome, or neither.

Conclusion:

By exploring genes involved in the etiology of craniosynostosis, we hope to understand gene mutations that may contribute to a patients' history of craniosynostosis. Future studies could focus on gathering more information from neonatal and pediatric patients at CHKD who also have a craniosynostosis diagnosis. Further analysis of these patients may help us explore connections between different gene mutations and craniosynostosis and identify screening measures for the improved identification and treatment of children with these genetic mutations.