Case: Patient AUS1-IV:1, 21yo, female, Australia

CasePresentingHPOs: HP:0030917, HP:0008947, HP:0004323, HP:0002091, HP:0002650, HP:0003306, HP:0003701, HP:0003691, HP:0005991, HP:0002058, HP:0000268, HP:0003458 (low APGAR score, early hypotonia, abnormality of habitus, restrictive lung disease, scoliosis, spinal rigidity, proximal muscle weakness, scapular winging, limited neck flexibility, myopathic face, dolichocephaly, Myopathic electromyogram)

HPOsFreeText: born at term, mild meconium aspiration, crawled at 10mo, walked at 18mo, thin body habitus, required nocturnal non-invasive ventilation at 13yo, required posterior spinal fusion at 3rd thoracic vertebra and 5th lumbar vertebra at 15yo, normal cardiac function, normal creatine kinase (at 13yo = 188 IU/l)

Muscle biopsy showed variation in myofiber size with increase in internal nuclei and split myofibers, scattered nuclear bags, scattered subsarcolemmal inclusions up to 4 µm, moth-eaten and lobulated appearance of myofibers, normal phosphorylase, inclusions reactive with slow myosin resembling hyaline bodies and were shown to be composed of fine filamentous material

CaseNotHPOs: HP:0000602, HP:0100295 (ophthalmoplegia, muscle fiber degeneration)

FamilyInfo: Pedigree in Fig. 2, consanguineous (first-cousin) parents, Middle Eastern ancestry, no family history of neurological or cardiac abnormalities, there were 2 miscarriages prior to the proband

CasePreviousTesting:

CaseGenotypingMethod: Individuals IV:1 and IV:3 had NGS of 464 neurogenetic disease genes, Sanger sequencing to confirm recessive inheritance (confirmed heterozygosity in parents)

InheritancePattern: autosomal recessive

DiseaseEntity: n/a

Variant: NM_000257.4(MYH7):c.5134C>T (p.Arg1712Trp), homozygous

ClinVar: 14118, https://www.ncbi.nlm.nih.gov/clinvar/variation/14118/

gnomAD: n/a