Hartsfield syndrome ... (Hartsfield syndrome) - Gen FGFR1
Hartsfield syndrome (or Hartsfield-Bixler-DeMyer syndrome) is a rare condition characterized by holoprosencephaly (an abnormality of brain development), along with a malformation of the hands and feet known as ectrodactilia.
In early development, before birth, the brain is usually divided into two halves, the right and left hemispheres. Holoprosencephaly occurs when the brain does not divide properly. In the most severe forms of holoprosencephaly, the brain is not divided at all. These affected individuals have a central eye (ciclopía) and a tubular nasal structure located above the eye (proboscis). Most newborns with severe holoprosencephaly die before birth or shortly thereafter. In less severe cases of holoprosencephaly, the brain is partially divided. The life expectancy of these people affected depends on the severity of signs and symptoms.
Often people with Hartsfield syndrome have other brain abnormalities associated with holoprosencephaly. Affected individuals may have a malfunction of the pituitary gland. Because pituitary dysfunction causes partial or total lack of these hormones can cause a variety of disorders. These include diabetes insipidus, which alters the balance between fluid intake and urine excretion; one growth hormone deficiency, leading to stunting; and hypogonadotropic hypogonadism, which affects the production of hormones that direct sexual development. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature patterns and sleep. In addition, people with Hartsfield syndrome have mild to severe developmental delay.
The other essential feature of Hartsfield syndrome is ectrodactilia. The ectrodactilia causes a limb deformity in which there are no parts or whole digits and often sindactilia. Other features described in people with Hartsfield syndrome include craniosynostosis, heart defects, Vertebral and abnormal genitalia. Some affected individuals have distinctive facial features including hypertelorism or hypotelorism, abnormally small ears in size or unusually shaped and cleft lip with or without cleft palate.
Hartsfield syndrome 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 development and growth of various parts of the body, including the brain, craniofacial bones and the bones of the hands and feet.
At least seven mutations have been identified in the FGFR1 gene in people with Hartsfield syndrome. Some of these mutations affect one of the two copies of the FGFR1 gene in each cell, resulting in an autosomal dominant disease. It is believed that these mutations have a "dominant negative" effect, meaning that the version of the FGFR1 protein encoded from the mutated copy of the gene interferes with the activity of the version of the protein from the normal copy of the gene . In other cases, the mutations occur in both copies of the FGFR1 gene, resulting in autosomal recessive disease. All mutations associated with syndrome Hartsfield greatly reduce or eliminate the function of FGFR1 protein, including their ability to bind FGFs. As a result, the receiver is not able to transmit signals properly, which affects many aspects of normal development. However, it is unclear how these changes result in holoprosencephaly and ectrodactilia specifically, the characteristic features of Hartsfield syndrome.
Hartsfield syndrome can be inherited in an autosomal dominant or autosomal recessive pattern. Autosomal dominant inheritance means that a copy of the altered gene in each cell is sufficient to express the process. In these cases, the syndrome is usually due to mutation in the FGFR1 gene that occurs during the formation of reproductive cells or early embryonic development. Most of these affected individuals have no history of the disease in his family. However, in a small number of cases, people with Hartsfield syndrome have inherited the altered gene from an affected parent has a mutation in the gene FGFR1 only in reproductive cells, a phenomenon known as germinal mosaicism. Less often, Hartsfield syndrome is inherited in an autosomal recessive pattern, which means that 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 syndrome Hartsfield, 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).