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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Agenesis of corpus callosum	Very frequent (present in 80%-99% of cases)
Intellectual disability, severe	Very frequent (present in 80%-99% of cases)
Microcephaly	Very frequent (present in 80%-99% of cases)
Seizures	Very frequent (present in 80%-99% of cases)
Severe global developmental delay	Very frequent (present in 80%-99% of cases)
Spasticity	Very frequent (present in 80%-99% of cases)
Abnormal hair pattern	Frequent (present in 30%-79% of cases)
Abnormality of the hip bone	Frequent (present in 30%-79% of cases)
Coarse facial features	Frequent (present in 30%-79% of cases)
Generalized hirsutism	Frequent (present in 30%-79% of cases)
Nystagmus	Frequent (present in 30%-79% of cases)
Protruding ear	Frequent (present in 30%-79% of cases)
Scoliosis	Frequent (present in 30%-79% of cases)
Strabismus	Frequent (present in 30%-79% of cases)
Cerebral cortical atrophy	Occasional (present in 5%-29% of cases)
Hypospadias	Occasional (present in 5%-29% of cases)
Inguinal hernia	Occasional (present in 5%-29% of cases)
Renal dysplasia	Occasional (present in 5%-29% of cases)
Renal hypoplasia/aplasia	Occasional (present in 5%-29% of cases)
Tetraplegia	Occasional (present in 5%-29% of cases)
Broad alveolar ridges	-
Cryptorchidism	-
High palate	-
Hirsutism	-
Hyperconvex nail	-
Intellectual disability, progressive	-
Large eyes	-
Limb joint contracture	-
Low anterior hairline	-
Neonatal hypotonia	-
Optic atrophy	-
Overlapping toe	-
Prominent supraorbital ridges	-
Spastic tetraplegia	-
Synophrys	-
Tapered finger	-
Visual impairment	-
X-linked inheritance	-

Last updated: 8/1/2017

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

Do you have updated information on this condition? Let us know.

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
1010 Wayne Avenue, Suite 650
Silver Spring, MD 20910
Toll-free: (800) 433-5255
Telephone: (301) 565-3842
Fax: (301) 565-3843 or (301) 565-5342
E-mail: info@thearc.org
Website: http://www.thearc.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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.

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

IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

GARD Answers GARD Answers

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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.