X-Linked Spondyloepiphyseal Dysplasia Tarda

CLINICAL DESCRIPTION

In adults, X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is characterized by disproportionately short stature with short trunk and arm span significantly greater than height. At birth, affected males are normal in length and have normal body proportions. Affected males exhibit linear growth deficiency beginning around age six to eight years. Final adult height is typically 137-163 cm. Progressive joint and back pain with osteoarthritis ensues; hip, knee, and shoulder joints are commonly involved but to a variable degree. Hip replacement is often required as early as age 40 years. Interphalangeal joints are typically spared. Motor and cognitive milestones are normal.

DIAGNOSIS/TESTING: The clinical diagnosis of X-linked SEDT can be established in a male proband with characteristic radiographic findings (which typically appear prior to puberty) including: multiple epiphyseal abnormalities, platyspondyly with characteristic superior and inferior "humping" seen on lateral view, scoliosis, hypoplastic odontoid process, short femoral necks, and coxa vara; evidence of premature osteoarthritis appears in young adulthood. The molecular diagnosis of X-linked SEDT can be established in a male proband with suggestive findings and a hemizygous pathogenic variant in identified by molecular genetic testing. The molecular diagnosis of X-linked SEDT can be established in a female proband with osteoarthritis and a heterozygous pathogenic variant in identified by molecular genetic testing.

MANAGEMENT

Treatment for scoliosis and kyphoscoliosis per orthopedic surgeon; surgical intervention may include spine surgery (correction of scoliosis or kyphosis). Pain management as needed for osteoarthritis; joint replacement (hip, knee, shoulder) as needed. : Cervical spine films prior to school age and before any surgical procedure involving general anesthesia to assess for clinically significant odontoid hypoplasia. Annual follow up for assessment scoliosis and joint pain. Extreme neck flexion and extension in individuals with odontoid hypoplasia. Activities and occupations that place undue stress on the spine and weight-bearing joints. Presymptomatic testing in males at risk may obviate unnecessary diagnostic testing for other causes of short stature and/or osteoarthritis.

GENETIC COUNSELING

By definition, X-linked SEDT is inherited in an X-linked manner. When performed, molecular genetic testing of all mothers of affected sons determined that regardless of family history all were carriers of a pathogenic variant in . Carrier females are at a 50% risk of transmitting the pathogenic variant in each pregnancy: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and will not be affected. None of the sons of an affected male will be affected; all daughters will be carriers of the pathogenic variant. Carrier testing of at-risk female relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variant in the family has been identified.