The Genetic Link between Phocomelia, Endometrial Stromal Sarcoma and Dysplastic Marrow: A Case Study

Background: Phocomelia is a malformation of the upper limbs, which can occur from various causes such as genetics, spontaneous mutation, and in utero teratogenic exposure (e.g., thalidomide). It is often associated with other congenital malformations. Myelodysplastic syndrome (MDS) signifies ineffective hematopoiesis. Patients are often asymptomatic and diagnosed through an incidental finding. However, there is risk of progression to myeloid leukemia for which a bone marrow transplant is needed for cure. Endometrial stromal sarcoma (ESS) is a rare, malignant uterine tumor most often seen in women 40 to 55 years of age. It is characterized by myometrial invasion with polymenorrhagia at presentation. Case Information: We report a case of phocomelia, MDS, and ESS in a pediatric patient, which demonstrates the impact a genetic link can have in clinical management. Patient is a 20-year-old female with phocomelia of the upper extremities. She presented with dysfunctional bleeding, which was thought to be secondary to uterine fibroids. An MRI was performed for evaluation and revealed a uterine sarcoma. Pre-operative screening revealed pancytopenia with intermittently persistent thrombocytopenia and dysplastic marrow with suspected MDS. Conclusions: With the presentation of three seemingly unrelated disorders, it is important to consider an underlying genetic link. There was suspicion that a chromosome 7 abnormality could link phocomelia, ESS and MDS, leading to a high risk of progression to leukemia. However, microarray analysis revealed a genetic mutation associated with thrombocytopenia absent-radius syndrome, which has a much lower likelihood of progression to bone marrow malignancy in the future.