Clinical characteristics: CHKB-related muscular dystrophy (CHKB-MD), reported in 47 individuals to date, comprises congenital muscular dystrophy (CMD) (44 individuals) and adolescent-onset limb-girdle muscular dystrophy (LGMD) (3 individuals).
CMD: All affected children have developmental delay and speech delay; gross motor milestones are delayed with subsequent loss of ambulation over time. Most have intellectual disability of varying severity; some have no speech. Autism spectrum disorder or attention-deficit/hyperactivity disorder is common. Dilated cardiomyopathy, seen in 14 children, resulted in death from heart failure in five and cardiac transplantation in one. Seizures are seen in some individuals. Ichthyosis is common.
LGMD: Motor development is normal; all affected children start walking at the usual age. Two affected individuals presented with rhabdomyolysis. One had mild intellectual disability. Behavior abnormalities and dilated cardiomyopathy were not observed.
Diagnosis/testing: The diagnosis of CHKB-MD is established in a proband with suggestive findings and biallelic loss-of-function pathogenic variants in CHKB identified by molecular genetic testing.
Management: Treatment of manifestations: There is no cure for CHKB-MD. Supportive care to improve quality of life, maximize function, and reduce complications typically involves multidisciplinary care by specialists in pediatric neurology, orthopedics, physical therapy, occupational therapy, developmental pediatrics, mental health, speech-language pathology, cardiology, dermatology, and clinical genetics.
Surveillance: Evaluations to monitor existing findings and assess for the emergence of new findings/concerns are intended to promote development, mitigate comorbidities, and optimize function while maximizing quality of life.
Agents/circumstances to avoid: Avoid strenuous exercise and viral infections, which may exacerbate muscle weakness.
Genetic counseling: CHKB-MD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a CHKB pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the CHKB pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.
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