Orofacial Botryomycosis: Oral Manifestations, Complications, And Management

Introduction

Andermann syndrome is a rare inherited disorder that affects the nerves that are related to sensory and motor functions. It is also called Charlevoix disease. This syndrome can also cause agenesis of the corpus callosum, which connects two hemispheres of the brain. A child affected by this syndrome starts walking at three to four years old and loses their ability to walk by their teenage years.

As they age, they develop contractures and joint deformities that cause restrictions in joint movements. They have symptoms such as absent reflexes, dull muscle tone, weak muscles, loss of sensation in the extremities, seizures, and intellectual disability. Individuals with Andermann syndrome have short life expectancies up to adulthood and have major complications due to respiratory insufficiency.

What Is Andermann Syndrome?

Andermann syndrome is a nerve disorder that damages the nerves of sensation and muscle movements; it occurs due to poor nerve development and is half their normal size. Agenesis (absence) or malformed corpus callosum, a thick nerve fiber bundle connecting the brain's right and left hemispheres, can occur in many people. This can also affect the functions of cranial nerves, which emerge from the brain and are attached to different parts of the head and neck.

Causes of Thinning Corpus Callosum:

• Sometimes, Corpus callosum is produced without the causes.

• Genetic inheritance of the people.

• Fetal alcohol syndrome and any damage or infection produced during the phase of pregnancy (12 to 24) to the fetus.

What Are the Clinical Features of Andermann Syndrome?

The clinical features may start to appear as a newborn or during pregnancy, and symptoms can vary among individuals, which include:

• Areflexia (absent reflexes).

• Hypotonia (dull muscle tone).

• Amyotrophy (asymmetric motor nerve damage of lower limbs, which results in muscle weakness and wasting).

• Severe weakness.

• Loss of sensation in the arms and legs.

• Tremors.

• Contractures (joint stiffness, which occurs due to muscle tightening).

• Scoliosis (sideward curve of the spine).

• Intellectual disability.

• Abnormal pigmentation of the retina.

• Seizures (uncontrolled brain activity that causes uncontrollable movements, behavior, or feelings).

• Absence of corpus callosum, which is a part of the brain.

• Craniosynostosis (early closure of the sutures, which fails in brain development).

• Myopia (nearsightedness, where the near objects are seen clearly but not the far ones).

• Hemiparesis (weakness in the body with loss of strength).

• Overall delays in developing speech, cognitive, emotional, and social skills.

• Psychiatric symptoms include hallucinations (perception of things that are not real), depression, paranoia (feeling of being threatened), agitation (feeling of restlessness), and anxiety.

• Physical features such as ocular hypertelorism (widely spaced eyes), brachycephaly (short head), high arched palate, and syndactyly (fused fingers).

• Due to cranial nerve defects, it can result in weakness of facial muscles, ptosis (droopy eyelids), and gaze palsy (inability to fix eyes in one direction).

• Strabismus (eyes that cannot look in one direction).

What Is the Cause of Andermann Syndrome?

Andermann syndrome occurs due to a mutation in the SLC12A6 (solute carrier family 12 member 6) gene. This gene is inherited and has an autosomal recessive pattern, where both parents carry one copy of the mutated gene each and are passed down to offspring. Still, parents are not affected by this condition.

Features of the SLC12A6 gene are:

• The SLC12A6 gene is located on chromosome 15.

• The SLC12A6 gene provides instructions for forming the KCC3 (K-Cl cotransporter) protein.

• The KCC3 protein helps in the co-movement of negatively charged chlorine ions and positively charged potassium ions across the cell membrane to maintain its electroneutral state.

• The KCC3 protein is important in the maintenance and development of nerve tissue and axons (a part of the nerve that helps transmit impulses).

• The KCC3 protein helps regulate chlorine, potassium, and water amounts in the intracellular spaces and cells.

• The KCC3 protein also helps in the function of other proteins that are involved in ion concentration.

• A mutation in the SLC12A6 gene can cause a lack of protein. It can interfere with the nerves that are involved in movement and sensation and also interfere with the development of the corpus callosum.

• A mutation in the SLC12A6 gene can cause other health conditions, such as Charcot-Marie-Tooth disease, an inherited disorder that damages the nerves.

What Is the Diagnosis of Andermann Syndrome?

The diagnosis of Andermann syndrome involves:

• Diagnosis is made through clinical, neuroimaging, electrophysiologic findings, and family history.

• Clinical findings involve the absence of reflexes, delays in development, and intellectual disability.

• Electrophysiological findings include the absence of sensory nerve action potentials in the median and ulnar nerves during the first year of life, diminished compound motor action potentials, and needle electromyography (a technique where a needle is inserted in the muscle to analyze its electrical activity) showing positive nerve degeneration.

• Neuroimaging using magnetic resonance imaging (MRI) scans shows a complete absence of corpus callosum in 60 percent of individuals, partial absence in 10 percent of individuals, and normal corpus callosum in 30 percent of individuals. Scanning also shows mild cerebellar or cortical atrophy in the next stage.

• Molecular genetic testing shows a mutation in the SLC12A6 gene. Molecular genetic testing involves a combination of comprehensive genomic testing and gene-targeted testing. Gene-targeted testing involves either single-gene testing, which is done to look for changes in one gene, or multigene panel testing, which is done to look for changes in many genes. Comprehensive genomic testing assesses hundreds of genes. It involves exome sequencing (a technique to sequence protein-coding regions of genes) or genomic sequencing (a technique to sequence entire genes).

What Is the Management of Andermann Syndrome?

• There is no cure for Andermann syndrome, but it involves managing a multidisciplinary team of pediatricians, pediatric neurologists, orthopedists, psychiatrists, occupational therapists, and physiotherapists. The management includes:

• Use of Valproate to manage seizures and behavioral problems.

• Physiotherapy improves mobility and reduces complications such as scoliosis and contractures.

• Surgical correction in cases of severe scoliosis.

• In cases of psychotic episodes, low-dose neuroleptics can be given.

Conclusion

Andermann syndrome is a rare, incurable disorder that requires family and social support. Genetic counseling among the individual's family should be done, and they should receive education about the inheritance and effects of the disorder. A genetic risk assessment should be done among the family members.