Pituitary hormone deficiency combined ... (Combined pituitary hormone deficiency -CPHD-) - Genes PROP1, POU1F1, HESX1, LHX3, LHX4, SOX2, SOX3, GLI2 and OTX2.

The combined deficiency of pituitary hormones (CPHD: Combined Pituitary Hormone Deficiency), also called congenital hypopituitarism, includes a heterogeneous characterized by affected growth hormone (GH) production alterations group and at least another of the hormones anterior pituitary as TSH, LH / FSH, PRL and, less frequently, ACTH. Clinical manifestations are summarized in features such as short stature, growth retardation, hypothyroidism, sexual problems, infertility and hypocortisolism development. Rarely, people with CPHD intellectual disabilities.As, a short, stiff neck, or underdeveloped optic nerves.

This process is due to mutations in at least nine genes. Mutations in the gene PROP1, located on the long arm of chromosome 5 long (5q35.3) are the most common known cause of CPHD, representing 12% to 55% of cases. They have identified mutations in other genes, each in a smaller number of individuals affected. These genes include POU1F1 (3p11), HESX1 (3p14.3), LHX3 (9q34.3), LHX4 (1q25.2), SOX2 (3q26.33), SOX3 (Xq27.1), GLI2 (2q14) and OTX2 ( 14q22.3). However, in most of the affected people they have not been identified mutations in genes known to be associated with this process. The cause of the disease in these individuals is unknown.

Genes associated with combined pituitary hormone deficiency (CPHD) encoding transcription factors, which help to control the activity of many other genes. The proteins are involved in the development of the pituitary gland and differentiate their cell types. The cells of the pituitary gland are responsible for triggering the release of several hormones that direct the development of many parts of the body. Some transcription factors are found only in the pituitary gland, while some are also active in other parts of the body.

Mutations in these genes can lead to abnormal cell differentiation of the pituitary gland and may inhibit the production of various hormones. These hormones may include growth hormone (GH), which is necessary for normal growth; follicle stimulating hormone (FSH) and luteinizing hormone (LH), which play a role in both sexual development and fertility; stimulating hormone (TSH), which helps with the function of the thyroid gland; prolactin, which stimulates the production of breast milk; and adrenocorticotropic hormone (ACTH), which influences the energy production in the body and maintains normal levels of blood glucose and blood pressure. The extent to which these hormones are deficient is variable, ACTH and prolactin showing greater variability. In many affected individuals, ACTH deficiency does not occur until late adulthood.

Mutations in the gene PROP1 are most often associated with CPHD. They have identified at least 25 PROP1 gene mutations in affected individuals. Mutations most frequently found, are located in exon 2. These genetic changes include deletions [301-302delAG] and, less frequently, [149delAG] that cause a change in the reading frame and lead to a truncated protein functionless. Therefore, patients with any of them have a phenotype of severe CPHD suffer NPPP are short and are deficient in GH and TSH before the age of ten years old and then Gonadotropin deficiencies. ACTH deficiencies in these cases usually occur after the third decade of life.

Mutations in the gene lead to LHX3 GH deficiencies, TSH, PRL and gonadotropin - associated cervical spine short and limited rotation of the neck. Furthermore, mutations that occur in the gene LHX4 cause abnormalities in the cerebellum and GH deficiencies, TSH and ACTH. Defects in the gene POU1F1 cause deficiencies in GH, PRL and TSH and those occurring in the PROP1 gene can cause deficiencies in all pituitary hormones produced by POU1F1 dependent cell lines and in gonadotropins and in corticotropins.

As we see, mutations of patients on factors Pituitary transcription (PTF) are highly variable, but from recent studies using magnetic resonance imaging (MRI) can get an idea about what PTF is more likely that the mutation occurs. Thus, mutations in LHX4 are usually associated with PPE (Erythropoietic protoporphyria); those occurring in PROP1 and LHX3 associated with NPPP (Neutrophils, platelets, and platelet poor plasma); while those corresponding to HESX1 may be associated with both EPP as NPPP.

Most cases are sporadic CPHD, meaning that occur in people with no history of disease in your family. Less often, CPHD described in families. In these cases, CPHD may have an autosomal dominant pattern of inheritance or autosomal recessive. Autosomal dominant inheritance means that a copy of an altered gene in each cell is sufficient to express the disease. Autosomal recessive inheritance means 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. Most inherited cases of combined pituitary hormone deficiency is inherited in an autosomal recessive pattern.

Tests in IVAMI: in IVAMI perform the detection of mutations associated with combined deficiency of pituitary hormones (CPHD), by complete PCR amplification of the exons of PROP1, POU1F1, HESX1, LHX3, LHX4, SOX2, SOX3 genes, GLI2 and OTX2, respectively, and subsequent sequencing. It is recommended to start PROP1 study by the gene responsible for most cases, with the possible reduction of time and cost involved in most cases. If not found the mutation in this gene, it offers the possibility of completing the study by those genes with greater frequency of mutations.

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).

Or impregnated card with dried blood sample (IVAMI can mail the card to deposit the blood sample).