The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5 untranslated region, which hybridizes to the complementary CGG-repeat portion of the FMR1 gene to form an RNA·DNA duplex.A subset of people with intellectual disability and symptoms resembling fragile X syndrome are found to have point mutations in FMR1. This subset lacked the CGG repeat expansion in FMR1 traditionally associated with fragile x syndrome. Inheritance
Fragile X syndrome has traditionally been considered an X-linked dominant condition with variable expressivity and possibly reduced penetrance. However, due to genetic anticipation and X-inactivation in females, the inheritance of Fragile X syndrome does not follow the usual pattern of X-linked dominant inheritance, and some scholars have suggested discontinuing labeling X-linked disorders as dominant or recessive. Females with full FMR1 mutations may have a milder phenotype than males due to variability in X-inactivation.Before the FMR1 gene was discovered, analysis of pedigrees showed the presence of male carriers who were asymptomatic, with their grandchildren affected by the condition at a higher rate than their siblings suggesting that genetic anticipation was occurring. This tendency for future generations to be affected at a higher frequency became known as the Sherman paradox after its description in 1985. Due to this, male children often have a greater degree of symptoms than their mothers.The explanation for this phenomenon is that male carriers pass on their premutation to all of their daughters, with the length of the FMR1 CGG repeat typically not increasing during meiosis, the cell division that is required to produce sperm.
It remains unclear how a reduced amount of this protein disrupts early development and causes the characteristic features of Greig cephalopolysyndactyly syndrome.This condition is inherited in an autosomal dominant pattern, which means the defective gene is located on an autosome, and only one copy of the defective GLI3 gene is sufficient to cause the disorder. In cases of dominant inheritance, an affected person inherits the genetic mutation or chromosomal abnormality from one affected parent.Rare instances of this disorder are sporadic, and occur in people with no history of the condition in their family. Diagnosis
The disease is not easily definable. The main form of diagnosis is presumptive, if the person has the usual triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, macrocephaly, and  hypertelorism. However, a definitive diagnosis can be made if there is a phenotype that is caused by a Gcps and a Gli3 gene mutation. It can also be made if the person has a family member or relative with the disease. Possibly, antenatal ultrasound can detect macrocephaly, and a high-resolution ultrasound can detect polydactyly and syndactyly. There are a lot of differential diagnoses, including over 100 syndromes and disorders that can cause polydactyly. However, there are a few diseases with an overlap that is significant. These diseases include: acrocallosal syndrome, carpenter syndrome, and Gorlin syndrome. Management
The main treatment is surgery to fix the abnormalities in the limbs, like syndactyly.