A High Prevalence Rate of Tibia Hemimelia in a Subregion of West Azarbaijan, Iran

From 1995 to 2017 an abnormally high number of tibia hemimelia (TH) patients from the
Maku subregion in the West Azarbaijan province of Iran were referred to our orthopedic
department for treatment. Regarding the occurrence of TH in many families in a restricted
region and negative results of available genetic tests, we hypothesized that a founder
mutation etiology that is different from previous known genetic disorders might produce
the trait of TH in our patients. Through a retrospective study, we collected demographic
data including date of birth, patients and parents place of birth, sex, type of TH, presence of
other musculoskeletal anomalies, and treatment from the patients who were referred to
our department. We obtained a blood sample for genetic studies. We carried out genetic
studies in cytogenetics andmolecular levels on a patient with familial TH. The prevalence of
TH in theMaku subregion ofWestAzarbaijanwas 149.5 (95% confidence interval [CI]: 68.4–
283.8) per 1 million live birth. The patients did not fit with any known syndromes with TH.
Genetic evaluations of a patient with familial history of TH in this case series exhibited no
detectable change in both cytogenetic and molecular levels. There was an obvious
increased prevalence rate of TH in this province and particularly in the Maku subregion.
The cytogenetic locations for known syndromic TH are not responsible for the observed
anomalies in our patients. Our next step for detecting possible genetic mutations in our
patients would be mutation analysis via very high-resolution whole genomic sequencing in
more patients or genetic linkage study.