Molecular Characteristics: MYO18B encodes a class XVIII myosin that is mainly expressed in cardiac and skeletal muscles and in somites. The encoded protein is proposed to influence intracellular trafficking and participate in a delicate process of integrating thick and thin filaments into the sarcomere.
Mutations and pathophysiology
Zebrafish knockout models for myo18b showed disorganized accumulation of actin, myosin, and α-actinin and loss of sarcomere organization in striated muscles.
Altuame et al. summarized the reported cases of MYO18B-related syndrome. A few selected examples of pathogenic variants in MYO18B are mentioned below:
Malfatti et al. (2015) reported a homozygous c.6496G>T; p.Glu2166* in a Portuguese patient who died of cardiomyopathy at an early age. Muscle weakness was present in addition to high-arched palate and low set ears.
Brunet et al. (2020) reported a homozygous c.6433C>T, p.(Arg2145*) in a patient of Afghani ancestry. The patient had the classical picture of Klippel-Feil anomaly, muscle weakness, scoliosis, and facial dysmorphia (ptosis, bulbous nose, high-arched palate, low set ears, and low posterior hairline)
Altuame et al. (2021) reported 6 Arab patients (2 previously reported by Alazami et al. (2015)) with c.6905C>A;p.(Ser2302*) (homozygous) variant and one patient of Caucasian ancestry with c.6660_6670del;p.(Arg2220Serfs*74) (homozygous) variant. Five of the patients had the classical Klippel-Feil Syndrome 4 picture of Klippel-Feil anomaly, muscle weakness (more in the lower extremity), and variable facial dysmorphia (including ptosis, bulbous nose, high-arched palate, low set ears, and low posterior hairline). Two of the Arab patients did not have Klippel-Feil anomaly (however, one of them had fusion of thoracic vertebrae) and did not have facial dysmorphia. They did however have muscle weakness similar in character to other reported cases.
Hematoxylin and eosin stain of muscle fibers taken from MYO18B-related syndrome patients indicates myopathy, with moderate variation of fiber size. Atrophic and hypertrophic fibers and scattered dense bodies (reminiscent of the nemaline rods) can also be seen.
MYO18B