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 macrocephaly. Radiologic features include shortening of long bones with mild metaphyseal flare; narrowing of the inferior lumbar interpedicular distances; short, broad femoral neck; and squared, shortened ilia. The skeletal features are very similar to those seen in achondroplasia but tend to be milder. Medical complications common to achondroplasia (e.g., 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.
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. Suboccipital decompression if neurologic status is affected by spinal cord compression. Treatment for thoracolumbar kyphosis and/or genu varum as per orthopedic surgeon if necessary. Laminectomy relieves symptoms of spinal stenosis; about 70% of individuals experience relief of symptoms following decompression without laminectomy. Epilepsy is treated in the standard fashion. Developmental milestones are followed closely during early childhood so that cognitive impairments are addressed with special educational programs. Connect family with local resources and support.
Surveillance: Height, weight, and head circumference should be monitored using achondroplasia-standardized growth curves. The following should be performed at routine well-child visits: neurologic examination for signs of spinal cord compression, assessment of signs and symptoms of sleep apnea, physical examination for emerging leg bowing, and monitoring of development and social adjustment. MRI or CT examination of the foramen magnum is indicated if there is evidence of severe hypotonia, spinal cord compression, or central sleep apnea.
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. If the proband has a known FGFR3 pathogenic variant that cannot be detected in the leukocyte DNA of either parent and neither parent has an autosomal dominant skeletal dysplasia, the recurrence risk to sibs is estimated to be 1% because of the possibility of parental germline mosaicism. An individual with hypochondroplasia who has a partner of average stature is at a 50% risk of having a child with hypochondroplasia. If an affected individual's partner also has hypochondroplasia (or another dominant form of skeletal dysplasia), genetic counseling becomes more complicated because of (1) the risk for inheriting two dominantly inherited skeletal dysplasias, (2) the high incidence of genetic heterogeneity, and (3) the lack of medical literature addressing these circumstances. Prenatal testing and preimplantation genetic testing are possible if the causative pathogenic variant(s) have been identified in the affected parent(s).
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