⚕️🩺 ACONDROPLASIA: Genética, Síntomas, Diagnóstico y Tratamiento

Summary

Achondroplasia is a hereditary skeletal dysplasia characterized by rhizomelic dwarfism, brachydactyly, hyperlordosis, and macrocephaly. It is the most common form of dwarfism, with most cases arising from a de novo mutation. The condition is caused by mutations in the FGFR3 gene, and is inherited in an autosomal dominant pattern. Patients often experience motor delays, short stature, and skeletal abnormalities, along with potential complications such as hydrocephalus, apnea, and spinal cord compression. Diagnosis is clinical, with genetic testing to confirm mutations. While there is no cure, treatments such as growth hormones and limb elongation may be considered to manage symptoms.

Takeaways

• 😀 Achondroplasia is a hereditary disease characterized by rhizomelic dwarfism, brachydactyly, hyperlordosis, and macrocephaly.
• 😀 It is the most common form of non-lethal skeletal dysplasia, easily recognizable as a type of dwarfism.
• 😀 80% of individuals with achondroplasia have parents of normal height, with most cases caused by de novo mutations.
• 😀 The condition is inherited in an autosomal dominant manner, with complete penetrance and allelic heterogeneity.
• 😀 The most common mutation occurs in the FGFR3 gene, leading to a gain of function that inhibits cartilage growth.
• 😀 Clinical features include a large head, prominent forehead, short limbs, trident hands, and a short, curved spine.
• 😀 Complications include motor retardation, hydrocephalus, cervical-spinal compression, obstructive sleep apnea, and recurrent ear infections.
• 😀 The diagnosis is primarily clinical, confirmed by prenatal ultrasound, genetic testing, and postnatal evaluation.
• 😀 Differential diagnoses include hypochondroplasia, thanatophoric dysplasia, SADDAN syndrome, and achondro-hypochondroplasia complex.
• 😀 Treatment focuses on symptom management, including growth hormone therapy, limb lengthening surgery, and addressing complications like sleep apnea and infections.

Q & A

What is achondroplasia?

Achondroplasia is a hereditary condition characterized by rhizomelic dwarfism (shortened limbs), brachydactyly (short fingers), hyperlordosis (excessive curvature of the spine), and macrocephaly (an abnormally large head). It is the most common form of non-lethal skeletal dysplasia and the most easily recognizable type of dwarfism.

How is achondroplasia inherited?

Achondroplasia is inherited in an autosomal dominant manner. This means that an individual with one affected parent has a 50% chance of inheriting the mutation and developing the condition.

What is the most common cause of achondroplasia?

The most common cause of achondroplasia is a de novo mutation in the FGFR3 gene, which is usually related to advanced paternal age. This mutation involves a point mutation that causes a substitution of arginine for glycine at position 380.

What is the role of the FGFR3 gene in achondroplasia?

The FGFR3 gene encodes a receptor that binds to fibroblast growth factors and regulates bone growth. In achondroplasia, a mutation in this gene leads to a gain of function, inhibiting cartilage growth and causing the characteristic short bones of the condition.

What are the primary clinical features of achondroplasia?

The primary clinical features of achondroplasia include a large head (macrocephaly), prominent forehead, short limbs (rhizomelic dwarfism), trident hands, hyperlordosis (excessive inward curve of the spine), and a prominent abdomen. Intelligence is typically normal.

What are some of the complications associated with achondroplasia?

Complications of achondroplasia can include motor development delays, hydrocephalus, cervical-spinal compression, obstructive sleep apnea, recurrent otitis media (ear infections), and various orthopedic issues. These can lead to respiratory, hearing, and mobility challenges.

How is achondroplasia diagnosed?

Achondroplasia is diagnosed clinically through physical examination. Prenatal diagnosis is possible via ultrasound at 26 weeks of gestation. Postnatal diagnosis can be confirmed through genetic testing to detect the point mutation in the FGFR3 gene and radiologic studies to assess bone and skeletal abnormalities.

What are the differential diagnoses for achondroplasia?

The differential diagnoses for achondroplasia include hypochondroplasia (a milder form of dwarfism), thanatophoric dysplasia (a more severe skeletal dysplasia), SADDAN syndrome, and the achondro-hypochondroplasia complex.

What treatments are available for achondroplasia?

While there is no cure for achondroplasia, treatments focus on managing symptoms. These may include growth hormone therapy (though benefits are variable), limb lengthening surgery, orthopedic care, respiratory support for apnea, and caution with neck manipulation due to the risk of spinal cord compression.

What is the prognosis for individuals with achondroplasia?

The prognosis for individuals with achondroplasia depends on several factors. In childhood, there is an increased risk of mortality due to spinal cord compression and airway obstruction. However, individuals who survive infancy can live into adulthood with proper medical management, although they may face challenges such as orthopedic issues and respiratory complications.