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.