ESPE Abstracts

Case Report: Novel case of short stature and co-occurrence of SHOX gene mutation and Fanconi Anemia. Fanconi anemia (FA) is a rare congenital disorder caused by mutations in any of over 16 documented genes leading to chromosomal fragility. Patients may present with physical manifestations including short stature or upper limb deformities, hematologic manifestations including progressive pancytopenia, or oncologic manifestations including solid tumors. Short stature (>2 SD below mean) is a common finding in FA and thought to be multifactorial. Both endocrine abnormalities, including impaired spontaneous GH secretion and hypothyroidism, and specific genetic mutations IVS4, have been implicated and are associated with more severe height deficiencies. Of note, a less severe degree of short stature has been documented in FA patients without these abnormalities without a clear underlying cause. We present a novel case study of a 12-year-old male with Fanconi Anemia diagnosed at age 4 and short stature who was later found to have a co-occurring SHOX whole gene deletion. Mutations or deletions of the SHOX gene, located in the pseudodominant region of the X and Y chromosomes, have been implicated as a cause of short stature in patients with idiopathic short stature (ISS), and a cause of short stature and limb abnormalities in patients with Leri-Weill dyschondrosteosis (LWD) and Turner Syndrome. Previous co-occurrence of SHOX gene mutation and Fanconi Anemia has not been documented. Abnormalities in the SHOX gene may be partially responsible for short stature in patients with FA. Patient presented to us at 11.5 yrs of age for evaluation of short stature. Has a history of Fanconi’s anemia diagnosed at age of 4yrs, with poor weight gain and need for G-Tube feedings for 6 years. On examination patient was at −3.77 SD for height and −4.03 SD for weight, Tanner stage I, mild mesomelia, absent Madelung deformity, and otherwise normal examination. Biochemical evaluation was performed (Table 1), with low IGF-1 (−1.27SD) and whole gene deletion of SHOX gene. Bone age was delayed by 3 years. Growth hormone was initiated at 0.3 mg/kg/week and has been tolerated well. We continue to monitor patient’s growth and communicate frequently with hematology group following patient.