Proud syndrome

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

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.

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.

Inheritance

X-linked recessive inheritance

Proud syndrome is inherited in an X-linked recessive manner. 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.

Signs and symptoms

The most common signs and symptoms of Proud syndrome are:

• 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).

Proud syndrome usually occurs in males; when it occurs in females, the signs and symptoms are often less severe. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Agenesis of corpus callosum
• Intellectual disability, severe(Early and severe mental retardation)
• Microcephaly(Abnormally small skull)
• Seizure
• Severe global developmental delay
• Short stature(Decreased body height)
• Spasticity(Involuntary muscle stiffness, contraction, or spasm)

30%-79% of people have these symptoms

• Abnormal hair pattern(Abnormal distribution of hair)
• Abnormality of the hip bone(Abnormality of the hips)
• Coarse facial features(Coarse facial appearance)
• Generalized hirsutism(Excessive hairiness over body)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Protruding ear(Prominent ear)
• Scoliosis
• Strabismus(Cross-eyed)

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)
• Hypospadias
• Inguinal hernia
• Renal dysplasia
• Renal hypoplasia/aplasia(Absent/small kidney)
• Tetraplegia(Paralysis of all four limbs)

Diagnosis

Molecular Genetics Tests: Deletion/duplication analysis Sequence analysis of select exons Sequence analysis of the entire coding region Targeted variant analysis

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. 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.

NIH genetic and rare disease info

• NIH info on Proud syndrome

Proud syndrome is a rare disease.

Proud syndrome Resources
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