Normal growth is a hallmark of childhood health. Poor growth is one of the most common reasons for referral to a pediatric endocrinologist. Despite extensive evaluation, the vast majority of children with growth disorders do not receive an etiological diagnosis. A subset of these children with severe growth disorders likely have undiagnosed genetic causes of their poor growth. Without an understanding of the patient's underlying disease etiology, physicians are often at a loss as to how to counsel and treat these patients. Our work focuses on using bioinformatics searches of the electronic medical records to define clinical subgroups of growth disorders and then carefully clinically characterizing those patients in combination with genomic studies to identify novel genetic etiologies for these subgroups. We then perform follow up laboratory work as well as further physiological studies to gain a better understanding of the pathophysiological consequences of these genetic variants. Our ultimate goal is to provide targeted care for growth disorders based on the individual patient's specific pathophysiology. The current proposal focuses on three specific subgroups of patients: 1. Patients with growth hormone resistance, 2. Patients with resistance to insulin-like growth factor 1 (IGF-I), and 3. Patients with severe short stature inherited from a single parent. Patients meeting criteria for each of these subgroups are quite rare. To address this issue, we have formed the first multicenter collaborative group in the United States focused on studying growth disorders. This group consists of investigators at three of the leading pediatric networks in America: Cincinnati Children's Hospital Medical Center, Boston Children's Hospital, and The Children's Hospital of Philadelphia. Targeted bioinformatics searches of the electronic medical record systems will be performed at each of these hospitals to identify eligible patients. Patients will then be recruited for careful clinical characterization as well as acquisition of DNA samples. Whole exome sequencing and chromosomal microarrays will be performed to identify the genetic etiologies followed by translational laboratory studies to investigate the biological consequences of novel genetic variants. Pilot studies of targeted interventions based on etiologies will be performed.