Hypochondroplasia

Excerpt

Clinical characteristics: Hypochondroplasia is a skeletal dysplasia characterized by short stature; stocky build; disproportionately short arms and legs; broad, short hands and feet; mild joint laxity; and relative macrocephaly. Radiologic features include shortening of long bones with mild metaphyseal flare; a lack of widening or a narrowing of the lumbar interpedicular distances with shortening of the pedicle length and posterior scalloping of the vertebral bodies; short, broad femoral neck; and squared, shortened ilia. The skeletal features are similar to those seen in achondroplasia but tend to be milder. Medical complications common to achondroplasia (e.g., foramen magnum stenosis, spinal stenosis, tibial bowing, obstructive apnea) occur less frequently in hypochondroplasia, but intellectual disability and epilepsy may be more prevalent. Children usually present as toddlers or at early school age with decreased growth velocity leading to short stature and limb disproportion. Other features also become more prominent over time. Infants may present with temporal lobe seizures.

Diagnosis/testing: The diagnosis of hypochondroplasia is established in a proband with characteristic clinical and radiographic features. Identification of a heterozygous FGFR3 pathogenic variant known to be associated with hypochondroplasia can confirm the diagnosis and help distinguish hypochondroplasia from achondroplasia and other related skeletal dysplasias in individuals with overlapping phenotypes.

Management: Treatment of manifestations: Management of short stature in hypochondroplasia is influenced by parental expectations and concerns; one approach is to address these concerns rather than trying to treat the child. Foramen magnum stenosis, thoracolumbar kyphosis, genu varum, and spinal stenosis are management by orthopedists and neurosurgeons using similar strategies employed in achondroplasia. Seizures are treated in the standard manner. Developmental and educational support as needed. Connecting families with local resources and support is important.

Surveillance: The following should be performed at routine well-child visits: measurement and assessment of height, weight, and head circumference using hypochondroplasia-standardized growth curves; assessment for signs and symptoms of spinal cord compression, sleep apnea, thoracolumbar kyphosis, and leg bowing; development assessment and monitoring of all developmental domains including speech and language; audiology evaluation if speech and/or hearing concerns arise. Evaluation of social adjustment at well-child visits and then annually, most important during the grade-school years.

Pregnancy management: Vaginal deliveries are possible, although for each pregnancy, pelvic outlet capacity should be assessed in relation to fetal head size; epidural or spinal anesthetic can be used, but a consultation with an anesthesiologist prior to delivery is recommended to assess the spinal anatomy; spinal stenosis may be aggravated during pregnancy.

Genetic counseling: Hypochondroplasia is inherited in an autosomal dominant manner. The majority of individuals with hypochondroplasia have parents of average stature and have hypochondroplasia as the result of a de novo pathogenic variant. An individual with hypochondroplasia who has a reproductive partner of average stature has a 50% chance of having a child with hypochondroplasia. When the proband and the proband's reproductive partner have the same or different skeletal dysplasias, genetic counseling is more complex. In general, if both members of a couple have a dominantly inherited skeletal dysplasia, each child has a 25% chance of having average stature, a 25% chance of having the same skeletal dysplasia as the father, a 25% chance of having the same skeletal dysplasia as the mother, and a 25% chance of inheriting a pathogenic variant from both parents and being at risk for a potentially poor pregnancy outcome. It is not possible to provide information about prognosis for all at-risk offspring. If one parent has hypochondroplasia and the other parent is of average stature, has hypochondroplasia, or has another dominantly inherited skeletal dysplasia, prenatal and preimplantation genetic testing are possible if the causative pathogenic variant(s) have been identified in the affected parent(s).