Rare Rheumatology News

Disease Profile

Proud syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

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;

Categories

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

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]

Symptoms

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

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.

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.

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
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
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
Increased nail curvature
Nail overcurvature

[ more ]

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

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]

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

    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.

    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

      Organizations Providing General Support

        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

          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.

            References

            1. CORPUS CALLOSUM, AGENESIS OF, WITH ABNORMAL GENITALIA. OMIM. September 2013; https://www.omim.org/entry/300004.
            2. 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.
            3. ARX. Genetics Home Reference. August 2013; https://ghr.nlm.nih.gov/gene/ARX.
            4. Spasticity. MedlinePlus. February 2013; https://www.nlm.nih.gov/medlineplus/ency/article/003297.htm.

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