American journal of medical genetics. Part A · 2012
Meier-Gorlin syndrome: growth and secondary sexual development of a microcephalic primordial dwarfism disorder.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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de Munnik Sonja A, Otten Barto J, Schoots Jeroen, Bicknell Louise S, Aftimos Salim, Al-Aama Jumana Y, van Bever Yolande, Bober Michael B, Borm George F, Clayton-Smith Jill, Deal Cheri L, Edrees Alaa Y, Feingold Murray, Fryer Alan, van Hagen Johanna M, Hennekam Raoul C, Jansweijer Maaike C E, Johnson Diana, Kant Sarina G, Opitz John M, Ramadevi A Radha, Reardon Willie, Ross Alison, Sarda Pierre, Schrander-Stumpel Constance T R M, Sluiter A Erik, Temple I Karen, Terhal Paulien A, Toutain Annick, Wise Carol A, Wright Michael, Skidmore David L, Samuels Mark E, Hoefsloot Lies H, Knoers Nine V A M, Brunner Han G, Jackson Andrew P, Bongers Ernie M H F
Аннотация
Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recently, mutations in the ORC1, ORC4, ORC6, CDT1, and CDC6 genes, encoding components of the pre-replication complex, have been identified. This complex is essential for DNA replication and therefore mutations are expected to impair cell proliferation and consequently could globally reduce growth. However, detailed growth characteristics of MGS patients have not been reported, and so this is addressed here through study of 45 MGS patients, the largest cohort worldwide. Here, we report that growth velocity (length) is impaired in MGS during pregnancy and first year of life, but, thereafter, height increases in paralleled normal reference centiles, resulting in a mean adult height of -4.5 standard deviations (SD). Height is dependent on ethnic background and underlying molecular cause, with ORC1 and ORC4 mutations causing more severe short stature and microcephaly. Growth hormone therapy (n = 9) was generally ineffective, though in two patients with significantly reduced IGF1 levels, growth was substantially improved by GH treatment, with 2SD and 3.8 SD improvement in height. Growth parameters for monitoring growth in future MGS patients are provided and as well we highlight that growth is disproportionately affected in certain structures, with growth related minor genital abnormalities (42%) and mammary hypoplasia (100%) frequently present, in addition to established effects on ears and patellar growth.