Poster Number: M240


Göknur Haliloglu, MD, National Institutes of Health, Hacettepe University Faculty of Medicine, Sandra Donkervoort, MS, CGC, NINDS/DIR/CNP/NGB/NNDCS, Sibel Öz Yıldız, MD, Hacettepe University Faculty of Medicine, Ying Hu, MS, National Institutes of Health, Lynn Pais, MS, Broad Institute of MIT and Harvard, Üstün Aydıngöz, MD, Hacettepe University Faculty of Medicine, Carsten Bonnemann, MD, PhD, National Institutes of Health

Introduction: Recognition of distinctive patterns of muscle involvement on imaging studies as part of “deep phenotyping” is a helpful tool in the diagnostic pathway of patients with rare neuromuscular disease.

Aim: To describe whole-body muscle MRI findings in a patient with a novel biallelic homozygous missense variant (c.801G>A, p.Asn267Lys) in PAX7 (NM_002584.2).

Case presentation: An 8-year-old Turkish girl, with a history of decreased intrauterine movements, polyhdramniosis, low birth weight, ptosis and cyanosis at birth, presented at the age of 4 years-4 months with abnormal gait. Course was progressive and complicated with weakness involving axial, truncal and proximal muscle groups, swallowing difficulties, scoliosis and nocturnal hypoventilation syndrome. Parents were first cousins, family history was otherwise non-contributory. Physical examination revealed asthenic phenotype, bilateral ptosis, bulbous nose, high arched palate, retrognathia and myopathic face. Neck was tilted to the right side with limited lateral neck rotations on both sides. She had scoliosis, inability to flex the knees, right knee and foot ankle and bilateral achilles tendon contractures. She had upper and lower extremity proximal > distal weakness. Serum CK level and initial muscle biopsy evaluation at the age of 4 years-4 months from vastus lateralis showed very mild variation in fiber size with the preservation of normal polygonal structure of muscle fibers. Distribution of Type 1 and Type 2 fibers were normal on ATPase staining. Whole-body MRI at 6 years and 3 months of age revealed atrophy of bilateral sternocleidomastoid, paraspinal, gluteal, and thigh muscles, as well as mild thoracolumbar dextroscoliosis. Paraspinal muscle involvement comprised erector spinae at lumbar, thoracic and neck levels, and iliopsoas muscles on both sides. One and a half years later, MRI of both thighs showed marked atrophy of the adductor muscle groups and sartorius along with atrophy of the quadriceps and semitendinosus muscles on both sides. No edema or increased diffusion was identified. The pattern of fatty replacement resembled rough-textured brush strokes. Re-evaluation of the muscle biopsy showed absence of PAX7-positive cells.

Conclusions: Selective sternocleidomastoid, paraspinal and thigh muscle involvement will further help to differentiate early-onset myopathies within the emerging group of “primary satellite-cellopathies”, which includes biallelic PAX7 variants.