Proud syndrome

Title

Other Names:

New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum; Corpus callosum, agenesis of, with abnormal genitalia; ACC with abnormal genitalia; New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum; Corpus callosum, agenesis of, with abnormal genitalia; ACC with abnormal genitalia; Proud Levine Carpenter syndrome See More

Categories:

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Nervous System Diseases

Summary Summary

Proud syndrome is a rare neurological condition that is primarily characterized by severe intellectual disability, agenesis of the corpus callosum, seizures, and spasticity. It usually occurs in males; when it occurs in females, the signs and symptoms are often less severe. Proud syndrome is caused by changes (mutations) in the ARX gene and is inherited in an X-linked recessive manner. Treatment is based on the signs and symptoms present in each person.^[1]^[2]

Last updated: 7/1/2015

Symptoms Symptoms

The most common signs and symptoms of Proud syndrome are:^[1]^[2]

Agenesis of the corpus callosum
Severe intellectual disability
Seizures
Stiff and/or rigid muscles (spasticity)

Other features may include microcephaly (unusually small head), limb contractures, scoliosis, characteristic facial features, kidney malformations, and genital abnormalities (i.e. cryptorchidism, hypospadias).^[1]^[2]

Proud syndrome usually occurs in males; when it occurs in females, the signs and symptoms are often less severe.

Last updated: 7/1/2015

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Agenesis of corpus callosum		0001274
Intellectual disability, severe	Early and severe mental retardation Mental retardation, severe Severe mental retardation [ more ]	0010864
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Seizures	Seizure	0001250
Severe global developmental delay		0011344
Short stature	Decreased body height Small stature [ more ]	0004322
Spasticity	Involuntary muscle stiffness, contraction, or spasm	0001257
30%-79% of people have these symptoms
Abnormal hair pattern	Abnormal distribution of hair	0010720
Abnormality of the hip bone	Abnormality of the hips	0003272
Coarse facial features	Coarse facial appearance	0000280
Generalized hirsutism	Excessive hairiness over body	0002230
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Protruding ear	Prominent ear Prominent ears [ more ]	0000411
Scoliosis	Abnormal curving of the spine	0002650
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
5%-29% of people have these symptoms
Cerebral cortical atrophy	Decrease in size of the outer layer of the brain due to loss of brain cells	0002120
Hypospadias		0000047
Inguinal hernia		0000023
Renal dysplasia		0000110
Renal hypoplasia/aplasia	Absent/small kidney Absent/underdeveloped kidney [ more ]	0008678
Tetraplegia	Paralysis of all four limbs	0002445
Percent of people who have these symptoms is not available through HPO
Abnormally large globe	Increased size of eyes Large eyes [ more ]	0001090
Broad alveolar ridges		0000187
Cryptorchidism	Undescended testes Undescended testis [ more ]	0000028
Global developmental delay		0001263
High palate	Elevated palate Increased palatal height [ more ]	0000218
Hirsutism	Excessive hairiness	0001007
Hyperconvex nail	Nail overcurvature	0001795
Intellectual disability, progressive	Mental retardation, progressive Progressive mental retardation [ more ]	0006887
Limb joint contracture	Limb contractures	0003121
Low anterior hairline	Low frontal hairline Low-set frontal hairline [ more ]	0000294
Neonatal hypotonia	Low muscle tone, in neonatal onset	0001319
Optic atrophy		0000648
Overlapping toe	Overlapping toes Overriding toes [ more ]	0001845
Prominent supraorbital ridges	Prominent brow	0000336
Spastic tetraplegia		0002510
Synophrys	Monobrow Unibrow [ more ]	0000664
Tapered finger	Tapered fingertips Tapering fingers [ more ]	0001182
Visual impairment	Impaired vision Loss of eyesight Poor vision [ more ]	0000505
X-linked inheritance		0001417

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 11/1/2018

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Proud syndrome is caused by changes (mutations) in the ARX gene, which encodes a protein that regulates the activity of other genes. This protein is especially important during early embryonic development since it is thought to be involved in the formation of many different body structures such as the pancreas, testes, brain, and muscles used for movement (skeletal muscles). For example, the protein helps regulate the process by which cells mature to carry out specific functions (differentiation) within the pancreas, testes, and muscles. In the developing brain, it plays many different roles such as assisting with the movement of neurons to their final locations. Specific changes in the ARX gene impair the function of the protein, which may disrupt the normal development of many different parts of the body. This can lead to the many signs and symptoms associated with Proud syndrome.^[3]

Last updated: 7/1/2015

Inheritance Inheritance

Proud syndrome is inherited in an X-linked recessive manner.^[1] A condition is considered X-linked if the mutated gene that causes the condition is located on the X chromosome, one of the two sex chromosomes (the Y chromosome is the other sex chromosome). Women have two X chromosomes and men have an X and a Y chromosome.

In X-linked recessive conditions, men develop the condition if they inherit one gene mutation (they have only one X chromosome). Females are generally only affected if they have two gene mutations (they have two X chromosomes), although some females may rarely have a mild form of the condition if they only inherit one mutation. A woman with an X-linked recessive condition will pass the mutation on to all of her sons and daughters. This means that all of her sons will have the condition and all of her daughters will be carriers. A man with an X-linked recessive condition will pass the mutation to all of his daughters (carriers) and none of his sons.

Last updated: 7/1/2015

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

The treatment of Proud syndrome is based on the signs and symptoms present in each person. For example, spasticity may be treated with a variety of therapies including medications and/or physical therapy.^[4] Medications may be prescribed to help prevent and/or control recurrent seizures. Surgery may be required to treat certain physical abnormalities such as kidney or genital issues. Children with severe intellectual disability may benefit from special education services.

For personalized information about the treatment and management of Partington syndrome, please speak to a healthcare provider.

Last updated: 7/1/2015

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

National Organization of Disorders of the Corpus Callosum
PMB 363
18032-C Lemon Drive
Yorba Linda, CA 92886
Telephone: 714-747-0063
Fax: 714-693-0808
E-mail: info@nodcc.org
Website: http://www.nodcc.org
The Arc of the United States
1825 K Street, NW
Suite 1200
Washington, DC, DC 20006
Toll-free: 1-(800) 433-5255
Telephone: +1-202-534-3700
Fax: +1-202-534-3731
E-mail: info@thearc.org
Website: https://www.thearc.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Proud syndrome. This website is maintained by the National Library of Medicine.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Proud syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

The NIH Undiagnosed Diseases Network Expands
September 26, 2018

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

CORPUS CALLOSUM, AGENESIS OF, WITH ABNORMAL GENITALIA. OMIM. September 2013; http://www.omim.org/entry/300004.
Proud VK, Levine C, Carpenter NJ. New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum. Am J Med Genet. April 1992; 43(1-2):458-466.
ARX. Genetics Home Reference. August 2013; http://ghr.nlm.nih.gov/gene/ARX.
Spasticity. MedlinePlus. February 2013; http://www.nlm.nih.gov/medlineplus/ency/article/003297.htm.