Congenital cataract, facial dimorphism and neuropathy (Congenital cataracts, neuropathy and facial dysmorphism) - Gen CTDP1.

Congenital cataract, facial dysmorphia and neuropathy (CCFDN) is a rare common disorder that affects various parts of the body. It is characterized by congenital cataracts and other ocular abnormalities, as microphthalmia and nystagmus. Often, affected individuals, mainly men, have specific facial features become more evident as they reach adulthood. These features include a prominent midface, a big nose, prominent teeth, and a small lower jaw. The disease results in progressive damage to peripheral nerves, known as peripheral neuropathy. In the early years of life, affected individuals manifest weakness in the legs and arms, leading to delayed development of motor skills. In adolescence, these individuals develop sensory disturbances such as numbness and tingling, especially in the legs, causing significant difficulties with mobility in adulthood. Muscle weakness may also lead to skeletal abnormalities such as deformed hands and feet and abnormal curvature of the spine. In addition, affected individuals may have ataxia, tremors and dismetría. Some individuals have mild intellectual disability. Individuals with short stature have CCFDN, low weight, and reduced bone density.

A complication called rhabdomyolysis occurs in some people with CCFDN, usually after a viral infection or, rarely, during or after surgery. The destruction of muscle tissue releases myoglobin, which is processed by the kidneys and released into the urine. The presence of myoglobin causes the urine red or brown. Muscles can take up to a year to recover, and episodes may worsen muscle weakness caused by neuropathy.

This process is due to mutations in the gene CTDP1, located on the long arm of chromosome 18 (18q23). This gene encodes a protein called carboxifosfatasa 1. This protein helps regulate the activity of RNA polymerase II enzyme. The RNA polymerase II enzyme initiates the transcription process to direct the synthesis of proteins.

So far, we have identified a mutation in the gene CTDP1 in people with congenital cataract, facial dysmorphia and neuropathy (CCFDN). This mutation, IVS6 + 389C> T, alters the way in which the protein carboxifosfatasa 1. This mutation introduces a premature stop signal in encoding the protein is encoded, which results in a nonfunctional protein that can not regulate the transcription. A defective regulation of the transcription process affects the development and function of many parts of the body. However, it is not clear how the functional loss of carboxifosfatasa 1 results in the specific signs and symptoms of CCFDN.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with congenital cataract, facial dysmorphism and neuropathy (CCFDN), by complete PCR amplification of exons CTDP1 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).