Lipomatosis cranio-encephalic-cutaneous (Encephalocraniocutaneous lipomatosis) - FGFR1 Gen  

The brain-cranio-cutaneous lipomatosis (ECCL), previously known as Haberland syndrome, is a rare condition that mainly affects the brain, eyes and skin of the head and face. Most of the signs and symptoms of this disease are congenital and vary widely among affected individuals.

A distinctive feature of ECCL is the development of nevi psiloliparus. Some people with ECCL also have noncancerous tumors under the skin elsewhere in the head or face. Individuals with ECCL may also alopecia, hypoplasia or aplasia dermal and changes in skin pigmentation. The most common ocular abnormality in people with ECCL is a non - cancerous growth known as choristoma. These growths may be present in one or both eyes and can affect vision.

About two - thirds of people with ECCL have noncancerous fatty tumors inside the brain or spinal cord around known as lipomas and lipoma intracranial intraspinal, respectively. In addition, affected people also have a higher risk of developing glioma. Abnormalities in the brain and spinal cord associated with ECCL may result in convulsions, muscle tension and abnormal mental retardation; however, about one - third of affected individuals have normal intelligence.

This process is due to mutations in the gene FGFR1 (fibroblast growth factor receptor 1), located on the short arm of chromosome 8 (8p11.23) encoding the receptor of the fibroblast growth factor 1 (FGFR1). This receptor interacts with the fibroblast growth factors (FGFs) to activate signaling within cells. Signaling through the FGFR1 protein involved in many critical, such as cell division, cell growth regulation and cell maturation processes. This signaling is important for normal growth and development of various parts of the body, including the brain, craniofacial bones and the bones of the hands, feet, arms and legs.

Signaling through the FGFR1 protein plays a critical role in the formation, survival and migration of neurons in several brain areas. In particular, this signaling appears to be essential for producing neurons gonadotropin releasing hormone (GnRH). GnRH controls the production of several other hormones that direct the sexual development before birth and during puberty. These hormones are important for normal function of the ovaries in women and testes in men. In addition, FGFR1 also appears to play a role in olfactory neurons.

They have identified at least two mutations in the FGFR1 gene in people with brain-cranio-cutaneous lipomatosis (ECCL). FGFR1 gene mutations associated with ECCL modified amino acids in the protein FGFR1. These mutations are described as "gain of function mutations" because sobreactivan the receiver, triggering an abnormal signaling altering growth and cell division. Work is to determine how these signaling changes lead to tumor growth and other characteristics of ECCL.

In some people with ECCL, it has not identified any mutation of FGFR1 gene. In these cases, the reason for the development of the disease is unknown.

Mutations causing ECCL are not inherited, but occur randomly in that a cell during the early stages of development before birth. As the cells continue to grow and divide, some have the mutation cells and other cells, a condition known as mosaicism.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with brain-cranio-cutaneous lipomatosis (ECCL), by complete PCR amplification of the exons of the FGFR1 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).