How to cite this article: Schmidt H, Kammer B, Grasser M, Enders A, Rost I, Kiess W. 2007. Endochondral gigantism: A newly recognized skeletal dysplasia with pre- and postnatal overgrowth and endocrine abnormalities. Am J Med Genet Part A 143A:1868–1875.
Endochondral gigantism: A newly recognized skeletal dysplasia with pre- and postnatal overgrowth and endocrine abnormalities†
Article first published online: 6 JUL 2007
Copyright © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 143A, Issue 16, pages 1868–1875, 15 August 2007
How to Cite
Schmidt, H., Kammer, B., Grasser, M., Enders, A., Rost, I. and Kiess, W. (2007), Endochondral gigantism: A newly recognized skeletal dysplasia with pre- and postnatal overgrowth and endocrine abnormalities. Am. J. Med. Genet., 143A: 1868–1875. doi: 10.1002/ajmg.a.31839
- Issue published online: 25 JUL 2007
- Article first published online: 6 JUL 2007
- Manuscript Accepted: 25 MAR 2007
- Manuscript Received: 22 MAR 2007
- pre- and postnatal overgrowth;
- cartilage hyperplasia;
- absent subcutaneous fat;
- precocious puberty;
- insulin hypersensitivity;
- low IGF-I and GH
We report on a 3-year-old male, born at 34 weeks of gestation, with marked pre- and postnatal overgrowth, birth weight of 6,600 g, length of 61 cm, and head circumference of 38.5 cm. A striking phenotype was recorded at birth, which became more evident during the follow-up period. He had macrobrachycephaly, facial abnormalities, small thoracic cage, long trunk, deformed spine, rhizomelia, large hands and feets, absent subcutaneous fat, small umbilical hernia, inguinal hernias, and large joints with mild contractures. Hypoglycemic episodes and obstructive apnea complicated the neonatal period. During follow-up, overgrowth continued with a height of 146 cm (+11.65 SDS) and a weight of 39 kg (BMI 18.3 kg/m2) at 3.5 years. Endocrinological work-up disclosed extremely low levels of growth hormone, insulin-like growth factors, and insulin. What makes our patient unique is the association of marked prenatal overgrowth; unusual phenotype; skeletal dysplasia caused by accelerated endochondral ossification resulting in cartilage hyperplasia of the skull base and spine, and postnatal gigantism; and complete absence of subcutaneous fat. Other well-known overgrowth syndromes were excluded. We hypothesize that autocrine/paracrine growth factors could be the cause of excessive endochondral ossification. Alternately, activating mutations in transcription factors involved in both growth and endocrine/metabolic homeostasis could be responsible for this unusual phenotype. © 2007 Wiley-Liss, Inc.