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Cytochrome P450 oxidoreductase deficiency
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Reviewed March 2014
What is cytochrome P450 oxidoreductase deficiency?
Cytochrome P450 oxidoreductase deficiency is a disorder of hormone production. This condition specifically affects steroid hormones, which are needed for normal development and reproduction. The hormonal changes associated with cytochrome P450 oxidoreductase deficiency can affect the development of the reproductive system, skeleton, and other parts of the body. These signs and symptoms are usually present at birth or become apparent in early childhood.
The signs and symptoms of cytochrome P450 oxidoreductase deficiency vary from mild to severe. Signs and symptoms of mild cases can include a failure to begin menstruation by age 16 (primary amenorrhea), an inability to have biological children (infertility) in both men and women, and a condition called polycystic ovarian syndrome (PCOS). PCOS is characterized by a hormonal imbalance in women that can lead to irregular menstruation, acne, excess body hair (hirsutism), and weight gain.
People with moderate cases of cytochrome P450 oxidoreductase deficiency may have external genitalia that do not look clearly male or female (ambiguous genitalia), and they may have infertility. People with moderate cytochrome P450 oxidoreductase deficiency usually do not have skeletal abnormalities.
The severe form of cytochrome P450 oxidoreductase deficiency is sometimes called Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis. Hormonal changes in affected males and females lead to the development of ambiguous genitalia or other genital abnormalities, as well as infertility. Severe cases are also characterized by skeletal abnormalities, particularly involving bones of the head and face. These include premature fusion of the skull bones (craniosynostosis), a flattened mid-face, a prominent forehead, and low-set ears. Other skeletal abnormalities can include joint deformities (contractures) that limit movement; unusually long, slender fingers (arachnodactyly); bowing of the thigh bones; and radiohumeral synostosis, which is a bone abnormality that locks the elbows in a bent position. A blockage of the nasal passages (choanal atresia), intellectual disability, and delayed development are also associated with the severe form of the disorder.
Some women who are pregnant with fetuses affected by cytochrome P450 oxidoreductase deficiency experience mild symptoms of the disorder even though they themselves do not have the disorder. They may develop excessive body hair growth (hirsutism), acne, and a deep voice. These changes go away soon after delivery.
How common is cytochrome P450 oxidoreductase deficiency?
The prevalence of cytochrome P450 oxidoreductase deficiency is unknown. About 65 cases have been reported worldwide.
Researchers suspect that cytochrome P450 oxidoreductase deficiency is underdiagnosed and that mild cases of this disorder may be relatively common. Because the signs and symptoms can be difficult to detect, people with mild cytochrome P450 oxidoreductase deficiency may never come to medical attention.
What genes are related to cytochrome P450 oxidoreductase deficiency?
Cytochrome P450 oxidoreductase deficiency is caused by mutations in the POR gene. This gene provides instructions for making the enzyme cytochrome P450 oxidoreductase, which plays a critical role in the formation of steroid hormones. This group of hormones includes testosterone and estrogen, which are essential for normal sexual development and reproduction; corticosteroids, which are involved in the body's response to stress; and aldosterone, which helps regulate the body's salt and water balance.
Mutations in the POR gene reduce the activity of cytochrome P450 oxidoreductase, which disrupts the production of steroid hormones. Changes in sex hormones such as testosterone and estrogen lead to problems with sexual development before birth and at puberty. In a woman who is pregnant with an affected fetus, abnormal levels of sex hormones in the fetus may cause her to have mild, temporary signs and symptoms of cytochrome P450 oxidoreductase deficiency.
Cytochrome P450 oxidoreductase is also needed for the production of cholesterol. This substance has many essential functions both before and after birth, including roles in the production of steroid hormones and in the formation and growth of bones. Mutations in the POR gene can disrupt the production of cholesterol, which likely impairs normal bone formation in the severe form of cytochrome P450 oxidoreductase deficiency. Studies suggest that a molecule called retinoic acid also plays a role in the skeletal abnormalities found in severe cases. The breakdown of retinoic acid requires cytochrome P450 oxidoreductase; if a shortage of cytochrome P450 oxidoreductase prevents retinoic acid from being broken down, the resulting excess of that molecule can stimulate the abnormal growth and fusion of bones.
The skeletal abnormalities found in the severe form of this disorder can also result from mutations in another gene, FGFR2. Some researchers use the name Antley-Bixler syndrome to describe these features, whether they are caused by mutations in the POR gene or in the FGFR2 gene. Others use the name Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis for cases caused by POR gene mutations, reserving the name Antley-Bixler syndrome for cases caused by FGFR2 gene mutations.
Read more about the POR gene.
How do people inherit cytochrome P450 oxidoreductase deficiency?
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Where can I find information about diagnosis or management of cytochrome P450 oxidoreductase deficiency?
These resources address the diagnosis or management of cytochrome P450 oxidoreductase deficiency and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about cytochrome P450 oxidoreductase deficiency?
You may find the following resources about cytochrome P450 oxidoreductase deficiency helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for cytochrome P450 oxidoreductase deficiency?
What if I still have specific questions about cytochrome P450 oxidoreductase deficiency?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding cytochrome P450 oxidoreductase deficiency?
acne ; aldosterone ; arachnodactyly ; atresia ; autosomal ; autosomal recessive ; bone formation ; cell ; cholesterol ; congenital ; craniosynostosis ; cytochrome P450 ; deficiency ; disability ; enzyme ; fetus ; gene ; genitalia ; hirsutism ; hormone ; hyperplasia ; infertility ; joint ; menstruation ; molecule ; ovarian ; oxidoreductase ; phenotype ; polycystic ovarian syndrome ; prevalence ; puberty ; recessive ; reproduction ; stress ; syndrome ; testosterone
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (10 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.