Achondroplasia is a skeletal growth disorder commonly known as dwarfism. It is the most common bone dysplasia. It produces a very short and disproportionate stature, resulting in very short limbs.
The gene transmitting the disease has been located on chromosome 4p16.3. Its frequency in the population ranges from 1/20,000 to 1/30,000 live newborns.
Causes of achondroplasia
In most cases, achondroplasia is the result of a random, spontaneous, de novo mutation in parents who are completely normal. These parents have a low risk in another pregnancy of having another affected child.
Many studies show that when the father is older than 37 years, there is a higher risk of the child having this disease due to mutations that occur in the sperm over the years.
Achondroplasia is inherited in an autosomal dominant manner. An achondroplasia-affected parent with a normal partner has a 50% risk in each pregnancy of having a child with achondroplasia. If both parents have achondroplasia, the risk in the offspring is 25% of having a child with average height, 50% of having a child with achondroplasia, and 25% of having a child with homozygous achondroplasia (a condition that is fatal).
Prenatal diagnosis in pregnancies at risk for achondroplasia is possible when the disease-causing mutation has already been identified in the family.
Achondroplasia: symptoms
Most children can be diagnosed by clinical symptoms alone, but in practice specialists always request molecular demonstration of the disease on chromosome 4.
These children have a very short stature, below the 3rd percentile, a shortening of the proximal part of the upper and lower extremities (rhizomyelic dwarfism), short fingers, “trident” hand when open, limited elbow extension, genu varum or “bracketed” legs, joint instability in the knee and other joints, thoracolumbar kyphosis when small and lumbar hyperlordosis that appears after ambulation, large head with prominent forehead, little development of the nasal bridge with midfacial area “inward” offering a characteristic facial appearance.
Their muscle tone is low and psychomotor development is slower which causes them to walk alone later than other children, sometimes at 21 months of age.
IQ is normal unless hydrocephalus or a central nervous system complication occurs.
It is very important, both in children and adults, to monitor for obstructive sleep apnea due to the small airway they have, the hypertrophy of tonsils and adenoids that often develop in many cases and the poor innervation of the airway musculature with secondary hypotonia. Eustachian tube dysfunction with seromucous otitis often leads to hearing loss and impaired speech progression. In adults, narrowing of the lumbar spinal canal can produce alterations in gait or continence.
In outpatient visits to patients with dwarfism it is important to control weight, height, head circumference, thoracic circumference, assessment of the instability or not of the craniocervical junction, periodic neurological examinations, sometimes practice of CT or cranial MRI and polysomnography if there are alterations in the rhythm of sleep.
The approximate adult height is 131 +/- 5cm in males and 124 +/- 5cm in females. Obesity eventually becomes a major problem as it aggravates the underlying morbidity secondary to their disease.
It is important that people with achondroplasia avoid risky sports such as impact sports, collision sports, tumbling or the use of trampolines due to the instability of the craniocervical junction.
X-rays of these children show characteristic findings, especially with narrowing of the distance between the pedicles in the caudal vertebrae and short bones with thickened tubular areas.
Treatment for achondroplasia
Although stature is the most striking and sometimes the only thing that comes to mind, people affected by achondroplasia may need attention to many organs or devices.
From a ventriculoperitoneal shunt for hydrocephalus (fortunately in few cases) to transtympanic drains for persistent seromucous otitis, to adenoid reduction and tonsil removal for obstructive apneas, CPAP for persistent apneas in older children, neurosurgery if there is cervical stenosis with spinal cord involvement or osteotomies in the lower extremities if there are very marked varus tibiae.
Although there have been medical trials of hormonal treatment with growth hormone, the results are not good or encouraging to date and this treatment is not recommended.
Neither have any diet, vitamin supplements, or other therapies studied given effective results.
For more than 30 years, at the Hospital Universitari Dexeus, limb elongation has been practiced with lengthening of 15 cm per bone (30 cm total, 15cm in the tibia tibia and another 15cm in the femur) achieving a socially acceptable height; about 150cm as desirable. There are different techniques and methods of elongation and we can boast in our center of very good results with children when they get older (ICATME method). Not all parents, not all doctors, not all groups of parents accept stretching.
These patients need to be cared for by multidisciplinary teams, as experience and anticipation of their potential and different and varied problems is needed. Good socialization and psychological support of the child and family is very important and regular meetings with parent groups are very helpful. Genetic counseling should always be there.
Fortunately, research and progress in medicine do not cease and a clinical trial is being carried out to treat these patients with drugs. It consists of a drug to inhibit the inhibitor that prevents bone growth and restore bone growth. If the years show good results with little or no side effects, limb lengthening would probably stop or be reduced to selected cases or cases that do not respond to treatment or where it cannot be performed for some other reason. At the end of 2016 the phase 3 study starts.