Cephalopolysyndactyly Greig syndrome ... (cephalopolysyndactyly Greig syndrome) - Gen GLI3 and chromosome 7  

The cephalopolysyndactyly Greig syndrome is a disorder that affects the development of the limbs, head and face. The range of variability of the syndrome is very wide. It is often manifested primarily as polydactyly or deviation of the big toe, with or without syndactyly in hands and feet. Additional features include ocular hypertelorism, macrocephaly, and a high and prominent forehead. In rare cases, affected individuals may develop convulsive, developmental delay and intellectual disability.

This process is due to mutations in the GLI3 (GLI family zinc finger 3) gene, located on the short arm of chromosome 7 (7p14.1), which encodes the synthesis of GLI proteins that control gene expression, and therefore intervene growth, cell specialization, brain structure and limb. GLI proteins family act in the same molecular pathway that Sonic Hedgehog. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal formation of many organs and tissues before birth.

They have identified at least 120 GLI3 gene mutations as responsible for this syndrome. In some cases there are chromosomal abnormalities such as a deletion or rearrangement of genetic material in the region of chromosome 7 containing the GLI3 gene. At other times there is a translocation of genetic material between chromosome 7 and another chromosome. Other cases are due to the deletion of several genes, including GLI3, on the short arm of chromosome 7. The loss of multiple genes can result in the development of a more severe form of the disease called deletion syndrome genes contiguous Greig cephalopolysyndactyly. People with this form of the disease have developmental problems most characteristic in the limbs, head and face, along with seizures, developmental delay and intellectual disability. Genetic changes responsible cephalopolysyndactyly Greig syndrome inhibit a copy of the gene in every cell in coding any functional GLI3 protein. Consequently, only half the normal amount of this protein is available to control the expression of target genes during embryonic development. It is unclear how a reduced amount of the GLI3 protein alters the development of the limbs, head and face and leads to the characteristics of cephalopolysyndactyly Greig syndrome.

Mutations in the GLI3 gene described in people with various forms of polydactyl. They are described as isolated or nonsyndromic because polydactyl occurs without other signs and symptoms, such as brain or eye abnormalities hipertelorismo. In this respect, mutations in the GLI3 gene can result in two types of Polydactyly, called polidactilia postaxial A (PAP-A) and A / B (PAP-A / B), characterized by an additional finger side of the little finger. Another way of polydactyl called preaxial polidactilia type IV (DPP-IV), may also be due to mutations in the GLI3 gene. People with this type of polidactalia have extra digits next to the thumb or big toe (hallux) and cutaneous syndactyly. In addition, PPD-IV can also include additional digits in other positions in the hands or feet. Polidactilia pattern seen in PPD-IV is similar to the cephalopolysyndactyly Greig syndrome, which is believed to PPD-IV can be a very mild form of the syndrome.

The cephalopolysyndactyly syndrome Greig is inherited as an autosomal dominant pattern, which means that an impaired or absent from GLI3 gene in each cell copy is sufficient for manifestation of the syndrome, although it can also occur in individuals with no family history, responding this case spontaneous mutations.

Tests in IVAMI: in IVAMI perform detection of mutations associated with cephalopolysyndactyly syndrome Greig, by complete PCR amplification of the exons of the GLI3 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).