SRS is an earlier and relatively common clinically identifiable syndrome in SGA, subsequent clinical application with gene detection technology; more syndromes are known, including 3M syndrome. 3M syndrome is relatively rare, and we find that it is difficult to identify from SRS through clinical manifestations in our clinical experience, but requires genetic testing to determine. The problem has been noted by scholars for a long time. When SRS was studied using NH-CSS, it was found that the diagnostic rate of SRS was 76.7%. In this paper, we used the NH-CSS criteria to study the clinical coincidence rate of 3M syndrome, and found that 83% of patients with 3M syndrome can be diagnosed as clinical SRS, which is even higher than the SRS. NH-CSS is recently recognized as the standard with optimized sensitivity and specificity; it still showed difficult to identify the two diseases in clinical practice.
We believe that the high clinical similarity of the two diseases is mainly caused by ① The diagnosis criteria of the 2 diseases have the same main clinical manifestation, such as “Height/ weight at birth and after birth less than the same age, feeding difficulties, low BMI, typical face deformities (micrognathia, triangular-shaped face, forehead protruding, relatively enlarged head circumference)”, ②Other minor criteria share same symptoms, such as prominent heel, clinodactyly, male sexual dysfunction was showed in two diseases , and the skeletal deformity of 3M syndrome was not completely absent in SRS. Therefore, it is not easy to distinguish SRS or 3M syndrome for children without body asymmetry. ③Genetic detection is currently a differential method. While if they are not the classical pathogenic genes or gene detection negative, the diagnosis is still a challenge. At that time, we have to make clinical diagnosis. We recommended that 3M syndrome can be further differentiated when SRS is diagnosed clinically.
Since we propose that clinical diagnosis is basic and necessary, we explore why these syndromes are so similar? In addition to the same clinical manifestations described above, we also analyzed the two diseases from the following aspects. The results of clinical data have already fully demonstrated the homology of the two diseases. In genetic research, we found that many patients with 3M syndrome were born in Turkey and Arabia, where the marriage rate of close relatives was relatively high. It could explain that the heredity mode of 3M syndrome was autosomal recessive of CUL7, OBSL1, and CCDC8 gene mutations. Whereas patients with SRS had different inheritance, including autosomal recessive, autosomal dominant, X chromosome dominant and others . It has been found that 11p15 ICR1 LOM and UPD(7)mat are the most common epigenetic abnormalities and can diagnose about 60-70% of SRS patients. Although they are different pathogenic factors, both of them affect the expression of IGF2, which lead to intrauterine growth restriction [17,20]. On the other hand, both of them have an effect on GH-IGF1 axis. We conclude that from above researches, the two diseases may have the same pathway root.
Although the pathogenic mechanism is homologous, there are some phenotypic differences between the two syndromes. Because of intrauterine growth restriction, SGA, and postnatal growth retardation, the adult lifetime height of the two diseases is lower than those of normal peers. While the final height in 3M syndrome patients is lower than of SRS , we explained that above three gene changes in 3M syndrome influence the expression of three proteins, therefore affect the normal growth cycles of cells, but the epigenetic abnormality of SRS does not change the gene sequence, it affects the expression of growth-related proteins.
For the clinical management, the two diseases mainly adopt symptomatic treatment and regular follow-up [5,22]. At present, the treatment of height is still the most concern of the two diseases. When reviewed the literatures, we found that the level of IGF1 and GH in both diseases were generally normal, they were a lack of catch-up growth after birth. In the case report, it was found that both diseases were treated with GH which was suitable for SGA. The guideline pointed out SRS was the only syndrome to be included in the clinical trials of GH in short children born SGA and an indication for growth-promoting treatment under the SGA registered. The longitudinal study of Smeets et al.  showed that the therapeutic effect of GH on patient with SRS was parallel to patients with non-SRS SGA. After treatment, the patients with SRS had an average increase of 1.3SD. Due to the patients with 3M syndrome were born SGA, GH was also the main treatment in this group. Although the treatment effect of 3M syndrome is inferior to SRS, we consider the possibility of fewer cases, less clinical experience, and insufficient treatment. However, GH can still improve a certain degree of height from the treatment reported in the case of 3M syndrome [24-26].