FKBP14 Kyphoscoliotic Ehlers-Danlos Syndrome

CLINICAL CHARACTERISTICS: FKBP14 kyphoscoliotic Ehlers-Danlos syndrome (FKBP14-kEDS) is characterized by congenital muscle hypotonia and weakness (typically improving during childhood), progressive scoliosis, joint hypermobility, hyperelastic skin, gross motor developmental delay, myopathy, and hearing impairment. Most affected children achieve independent walking between ages two and four years. A decline of motor function in adulthood may be seen, but affected individuals are likely to be able to participate in activities of daily living in adulthood and maintain independent walking. Occasional features underlying systemic connective tissue involvement include aortic rupture and arterial dissection, subdural hygroma, insufficiency of cardiac valves, bluish sclerae, bladder diverticula, inguinal or umbilical herniae, and premature rupture of membranes during pregnancy. Rarer findings may include bifid uvula with submucous or frank cleft palate, speech/language delay without true cognitive impairment, and rectal prolapse. DIAGNOSIS/TESTING: Clinical diagnostic criteria rely on the finding of congenital muscular hypotonia AND congenital or early-onset kyphoscoliosis in addition to generalized joint hypermobility or further gene-specific and/or supportive clinical features. The diagnosis of FKBP14-kEDS is established in a proband by the identification of biallelic pathogenic variants in FKBP14 by molecular genetic testing. MANAGEMENT: Treatment of manifestations: In those with aortic dilation or vascular dissection, use of beta blockers may be considered; physical and occupational therapy to address age-dependent decline in muscular strength; standard treatment for severe scoliosis, clubbed foot, osteopenia/osteoporosis, refractive error, hearing impairment, and cleft palate. Surveillance: Blood pressure measurement at each visit; neurodevelopmental assessment at each visit until adolescence; evaluation by an orthopedic physician as clinically indicated but typically