MedGen

Bestrophinopathies, the spectrum of ophthalmic disorders caused by pathogenic variants in BEST1, are typically characterized by retinal degeneration. The four recognized phenotypes are the three autosomal dominant disorders: Best vitelliform macular dystrophy (BVMD), BEST1 adult-onset vitelliform macular dystrophy (AVMD), and autosomal dominant vitreoretinochoroidopathy (ADVIRC); and autosomal recessive bestrophinopathy (ARB). Onset is usually in the first decade (except AVMD in which onset is age 30 to 50 years). Slow visual deterioration is the usual course. Choroidal neovascularization can occur in rare cases. ADVIRC is also associated with panophthalmic involvement including nanophthalmos, microcornea, hyperopia, and narrow anterior chamber angle with angle closure glaucoma. [from GeneReviews]

The dystrophinopathies cover a spectrum of X-linked muscle disease ranging from mild to severe that includes Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy (DCM). The mild end of the spectrum includes the phenotypes of asymptomatic increase in serum concentration of creatine phosphokinase (CK) and muscle cramps with myoglobinuria. The severe end of the spectrum includes progressive muscle diseases that are classified as Duchenne/Becker muscular dystrophy when skeletal muscle is primarily affected and as DMD-associated DCM when the heart is primarily affected. Duchenne muscular dystrophy (DMD) usually presents in early childhood with delayed motor milestones including delays in walking independently and standing up from a supine position. Proximal weakness causes a waddling gait and difficulty climbing stairs, running, jumping, and standing up from a squatting position. DMD is rapidly progressive, with affected children being wheelchair dependent by age 12 years. Cardiomyopathy occurs in almost all individuals with DMD after age 18 years. Few survive beyond the third decade, with respiratory complications and progressive cardiomyopathy being common causes of death. Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness. With improved diagnostic techniques, it has been recognized that the mild end of the spectrum includes men with onset of symptoms after age 30 years who remain ambulatory even into their 60s. Despite the milder skeletal muscle involvement, heart failure from DCM is a common cause of morbidity and the most common cause of death in BMD. Mean age of death is in the mid-40s. DMD-associated DCM is characterized by left ventricular dilation and congestive heart failure. Females heterozygous for a DMD pathogenic variant are at increased risk for DCM. [from GeneReviews]

Infantile myofibromatosis is a rare mesenchymal disorder characterized by the onset of nodules in the skin, striated muscles, bones, and, more rarely, visceral organs. Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular lesions occur in about 50% of patients. Lesions may be solitary or multicentric, and they may be present at birth or become apparent in early infancy or occasionally in adult life (summary by Arcangeli and Calista, 2006). Genetic Heterogeneity of Infantile Myofibromatosis See also IMF2 (615293), caused by mutation in the NOTCH3 gene (600276). [from OMIM]

The Gustavson type of X-linked syndromic intellectual developmental disorder (MRXSG) is characterized by intrauterine growth retardation, microcephaly, hypotonia, and severe global developmental delay, usually resulting in death in infancy or early childhood. Affected males have profoundly impaired intellectual development with absent speech, poor reaction to stimuli, optic atrophy, deafness, seizures, spasticity, and restriction of the large joints. Female carriers are usually unaffected due to skewed X inactivation that silences the pathogenic allele, although 1 severely affected female has been reported (Johansson et al., 2024). [from OMIM]