Dual diagnoses in 152 patients with Turner syndrome: Knowledge of the second condition may lead to modification of treatment and/or surveillance.

Turner syndrome is a sex chromosome abnormality in which a female has a single X chromosome or structurally deficient second sex chromosome. The phenotypic spectrum is broad, and atypical features prompt discussion of whether the known features of Turner syndrome should be further expanded. With the advent of clinical whole exome sequencing, there has been increased realization that some patients with genetic disorders carry a second genetic disorder, leading us to hypothesize that a "dual diagnosis" may be more common than suspected for Turner syndrome. We report five new patients with Turner syndrome and a co-occurring genetic disorder including one patient with Li-Fraumeni syndrome, Li-Fraumeni and Noonan syndrome, mosaic trisomy 8, pathogenic variant in RERE, and blepharophimosis-ptosis-epicanthanus inversus syndrome. We also undertook an extensive literature review of 147 reports of patients with Turner syndrome and a second genetic condition. A total of 47 patients (31%) had trisomy 21, followed by 36 patients (24%) had one of 11 X-linked disorders. Notably, 80% of the 147 reported patients with a dual diagnosis had mosaicism for Turner syndrome, approximately twice the frequency in the general Turner syndrome population. This article demonstrates the potential for co-occurring syndromes in patients with Turner syndrome, prompting us to recommend a search for an additional genetic disorder in Turner patients with unusual features. Knowledge of the second condition may lead to modification of treatment and/or surveillance. We anticipate that increased awareness and improved diagnostic technologies will lead to the identification of more cases of Turner syndrome with a co-occurring genetic syndrome.

Congenital Amegakaryocytic Thrombocytopenia: A Case Series Indicating 2 Founder Variants in the Mississippi Band of Choctaw Indians.

Congenital amegakaryocytic thrombocytopenia is a rare disorder causing thrombocytopenia that progresses to pancytopenia and bone marrow failure if untreated. It is caused by variants in the MPL gene which encodes the thrombopoeitin receptor. In this report, we review 5 cases of congenital amegakaryocytic thrombocytopenia, all of whom belong to the Mississippi Band of Choctaw Indians. There are 2 common variants in these cases: R90X and R537W. One variant was previously reported only once and had unclear significance at that time. With these variants identified, we hope to improve screening that results in earlier diagnosis in the Choctaw population in the future.