What Is Anauxetic Dysplasia?
Anauxetic dysplasia is an uncommon genetic disorder caused by changes in the RMRP (ribonuclease mitochondrial RNA processing) gene. The main characteristic features of this condition are dwarfism (short stature) and other skeletal abnormalities, dental problems, hypermobility of the joints, mild intellectual disability, and distinguishing facial features like a prognathic chin, closely spaced eyes, an unusually large tongue, fewer teeth than normal, and flat or sunken looks in the middle of the face.
Individuals with this genetic disorder have unusually short limbs for their height, even before birth. In some individuals, spinal cord compression may occur due to dislocation of the bones at the uppermost part of the spine, leading to neurological symptoms including pain, numbness, weakness, coordination problems, tingling sensations, and paralysis. If the dislocation of the bones is severe, the spinal cord compression may cause the breathing muscles to paralyze, which can be life-threatening and even cause death.
The skeletal abnormalities seen in anauxetic dysplasia may include a rounded upper back with a kyphoscoliosis curve and a barrel-shaped chest. If kyphoscoliosis is not surgically corrected, the lungs can constrict and cause difficulty breathing. Other skeletal deformities include dislocation of the hips, exaggerated curvature of the lower back, and the soles of the child being in a convex position, making a rocker-bottom feet appearance.
What Is the Cause of Anauxetic Dysplasia?
Anauxetic dysplasia is caused due to mutation (changes) of the RMRP gene. The RMRP gene contains a noncoding RNA molecule, to which various other proteins attach to form an enzyme complex known as mitochondrial RNA-processing endoribonuclease, or RNase MRP. This enzyme involves various significant cell functions, like processing ribosomal RNA. Also, this type of RNA is linked with cell structures called ribosomes, which are responsible for assembling protein building blocks into proteins.
The RMRP gene mutations cause changes in the noncoding RNA generated from the gene. So, the RNase MRP enzyme contains noncoding RNA with abnormal changes, functioning poorly in its ribosomal RNA processing function. However, the proper mechanism of mutation is not clearly understood; the poor functioning of the enzyme may be responsible for the disruption of skeletal development, which may manifest as the signs and symptoms of anauxetic dysplasia.
Any changes, even in one of the RMRP genes that provides a signal for the production of a protein component of the RNase MRP enzyme complex, can lead to anauxetic dysplasia. Anauxetic dysplasia is generally inherited in an autosomal recessive pattern. The autosomal recessive pattern means both gene copies in each cell have changed. The mother and the father of an individual with an autosomal recessive disorder both should carry one copy of the defective gene. However, the individual's parents may not exhibit any signs and symptoms of this condition.
What Are the Symptoms of Anauxetic Dysplasia?
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Severe Short Stature - One of the characteristic features of anauxetic dysplasia is extremely short stature. The adult height of the individual with this condition will be below the average range, approximately under 100 centimeters (around 3 feet, 3 inches). Also, their height will be disproportionate, meaning different body regions will be shortened to differing extents.
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Microcephaly - Many individuals with anauxetic dysplasia have a smaller head size than normal individuals. This can be noted even in infancy and may contribute to characteristic anauxetic dysplasia facial features.
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Kyphoscoliosis - It is a condition causing deviation in the curvature of the spine in both a back-to-front and side planes. It is one of the most common clinical significance of anauxetic dysplasia.
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Decreased Teeth Count - Individuals with this condition may have an absence of few primary and permanent teeth, called hypodontia, or, in some cases, the complete absence of teeth can also occur, called anodontia.
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Orbital Hypertelorism - The distance between the two eyes will be much less when compared to average individuals, giving a very closely spaced eye appearance.
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Abnormalities of the Hands and Feet - Abnormalities in the size or shape of the hands and feet can occur in people with anauxetic dysplasia, such as short fingers or toes.
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Prognathic Chin - The chin will be abnormally prominent due to the increased mandible length.
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Difficulty in Breathing - The individuals with anauxetic dysplasia may have respiratory distress due to skeletal abnormalities. The sensation of respiratory distress is called dyspnea.
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Intellectual Disability - Some individuals with this condition may develop an intellectual disability during the developmental period. Their IQ (intelligence quotient) score will be below 70.
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Developmental Delay - Some individuals with anauxetic dysplasia may experience developmental delays, such as crawling, sitting, or walking. These can be due to skeletal abnormalities.
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Paresthesia - Abnormal sensations such as pricking, tingling, pins and needles feeling, or skin numbness with no apparent physical cause may occur due to spinal cord compression.
How Is Anauxetic Dysplasia Diagnosed?
The diagnosis of anauxetic dysplasia is completed based on the clinical evaluation, including the medical history and physical examination of the affected individuals.
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Imaging Test - X-rays are an essential tool to identify specific skeletal abnormalities specific to anauxetic dysplasia, such as bone shape and structure abnormalities.
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Genetic Testing - It is used to confirm the diagnosis of anauxetic dysplasia. With genetic testing, mutations in the RMRP gene responsible for anauxetic dysplasia can be identified.
What Is the Treatment for Anauxetic Dysplasia?
There is no permanent cure for anauxetic dysplasia. The main aim of the anauxetic dysplasia treatment is to address the presenting symptoms and associated complications. The treatment involves a multidisciplinary team involving pediatricians, orthopedic specialists, dentists, geneticists, and other healthcare professionals, which is necessary to properly treat individuals with anauxetic dysplasia.
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Regular Check-Up - Close monitoring of growth and development is necessary to evaluate for any potential complications that can arise shortly, such as scoliosis or joint problems.
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Symptomatic Treatment - The main aim of the treatment is to treat the presenting illness or complications associated with anauxetic dysplasia.
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Genetic Counseling - Proper counseling is required for affected individuals and their families to provide knowledge about the inheritance of anauxetic dysplasia and risk factors.
Conclusion:
Anauxetic dysplasia is a rare genetic disorder with characteristic features of inappropriate short status and skeletal abnormalities. This disorder is caused by a mutation in the RMRP genes, to which various other proteins attach to form an enzyme complex. Many individuals can live a normal lifespan. However, they may face difficulties in daily life. There is no permanent cure for this condition; however, treatment is required to prevent any complications and manage the presenting illnesses.
