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Author Notes:

Lorraine Potocki, M.D., F.A.C.M.G., Professor, Department of Molecular and Human Genetics. Baylor College of Medicine, Texas Children’s Hospital, 6701 Fannin Street, Suite 1560, Houston, TX 77030, Phone: 832-822-4290, Fax: 832-825-1515. Email: lpotocki@bcm.edu

We would like to thank the individuals and their families for their willingness to participate and for sharing their clinical data with us. We acknowledge the generous referral from the many physicians and genetic professionals who helped identify subjects for these studies.

Rachel Franciskovich: The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from molecular genetic testing offered in the Baylor Genetics Laboratories Claudia Soler-Alfonso: The Department of Molecular and Human Genetics at Baylor College of Medicine derives salary support from molecular genetic testing offered in the Baylor Genetics Laboratories Juanita Neira-Fresneda: No conflicts of interest Bonnie McCann-Crosby: No conflicts of interest James R. Lupski: Baylor College of Medicine (BCM) and Miraca Holdings have formed a joint venture with shared ownership and governance of the Baylor Genetics (BG), which performs clinical microarray analysis and clinical exome sequencing. J.R.L. serves on the Scientific Advisory Board of the BG. J.R.L. has stock ownership in 23andMe, is a paid consultant for Regeneron pharmaceuticals, and is a co-inventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from molecular genetic testing offered in the Baylor Genetics Laboratories. Lorraine Potocki: The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from molecular genetic testing offered in the Baylor Genetics Laboratories.

Subject:

Research Funding:

This work was supported in part by National Institute of Child Health and Human Development grants K08 HD01149 (to L.P.), and the National Human Genome Research Institute, National Heart, Lung, and Blood Institute (NHGRI/NHLBI) grant UM1HG006542 to the Baylor Hopkins Center for Mendelian Genomics (BHCMG); National Institutes of Neurological Disorders and Stroke (NINDS) grant R35 NS105078 to JRL; National Institute of Child Health and Human Development (NICHD)U54HD083092 to IDDRC Clinical Translational Core.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • growth hormone
  • hypoglycemia
  • Potocki-Lupski syndrome
  • short stature
  • POTOCKI-LUPSKI-SYNDROME
  • HYPOPLASTIC LEFT-HEART
  • SMITH-MAGENIS
  • CHROMOSOMAL MICROARRAY
  • DUPLICATION 17P11.2
  • DIAGNOSIS
  • DUP(17)(P11.2P11.2)
  • DISORDERS

Short stature and growth hormone deficiency in a subset of patients withPotocki-Lupskisyndrome: Expanding the phenotype ofPTLS

Tools:

Journal Title:

AMERICAN JOURNAL OF MEDICAL GENETICS PART A

Volume:

Volume 182, Number 9

Publisher:

, Pages 2077-2084

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Potocki–Lupski Syndrome (PTLS, MIM 610883), or duplication of chromosome 17p11.2, is a clinically recognizable condition characterized by infantile hypotonia, failure to thrive, developmental delay, intellectual disability, and congenital anomalies. Short stature, classified as greater than two standard deviations below the mean, has not previously been considered a major feature of PTLS. Retrospective chart review on a cohort of 37 individuals with PTLS was performed to investigate the etiology of short stature. Relevant data included anthropometric measurements, insulin growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), growth hormone (GH) stimulation testing, blood glucose levels, brain MRI, and bone age. Approximately 25% (9/37) of individuals with PTLS had short stature. Growth hormone deficiency (GHD) was definitively identified in two individuals. These two PTLS patients with growth hormone deficiency, as well as three others with short stature and no documented GHD, received growth hormone and obtained improvement in linear growth. One individual was identified to have pituitary abnormalities on MRI and had complications of hypoglycemia due to unrecognized GHD. Individuals with PTLS can benefit from undergoing evaluation for GHD should they present with short stature or hypoglycemia. Early identification of GHD could facilitate potential therapeutic benefit for individuals with PTLS, including linear growth, musculoskeletal, and in cases of hypoglycemia, potentially cognitive development as well.
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