case_images: PMC11747468_01
case_images: Clinical manifestations of the proband and his family members. (A) Facial features of the proband's gills experiment. (B) Manifestations of the external shoulder blade of the proband. (C) Manifestations of proximal upper limb muscle atrophy in the proband. (D) The manifestation of proximal lower limb muscle atrophy combined with gastrocnemius pseudohypertrophy in the proband. (E) The entire spine of the proband shows X-ray results of mild scoliosis. (F) MRI of the proband's bilateral lower limbs revealed widespread signal abnormalities in the thigh muscles, characterized by patchiness and high signal intensity in the T2WI fat suppression sequence. (G-I) The facial features of the proband's maternal grandmother (G), proband's mother (H), and proband's cousin's (I) bulging cheeks. (J-L) External shoulder blade phenotypes of proband's maternal grandmother (J), proband's mother (K), and proband's cousin (L).
case_images: fgene-15-1522203-g001.jpg
case_images: PMC11747468_01_fgene-15-1522203-g001.jpg
case_images: F1
case_images: Table 1). He displayed winged scapulae, muscle atrophy in the proximal limbs, and bilateral pseudohypertrophy of the calf muscles (Figures 1B-D). There were atrophy of the shoulder girdle muscles, including the deltoids, along with proximal limb muscle dystrophy affecting the biceps brachii, triceps brachii, and quadriceps femoris. He exhibited flushing, erythema, and hyperkeratosis on the palmar surface of both hands and feet (Supplementary Figure 1), indicative of Nagashima-type palmoplantar keratoderma (PPKN). X-rays of the spine revealed mild scoliosis (Figure 1E), while electromyography showed myogenic damage in the right biceps brachii and right rectus femoris muscles. On diffusion-weighted imaging (DWI), the signals were high or slightly high (Figure 1F). In the proband's family, there are four individuals: maternal grandmother, mother, aunt, and cousin, all exhibiting varying degrees of facial, shoulder, and/or limb muscle weakness symptoms (Figures 1G-L; Table 1).
case_images: Pedigree chromatograms of the identified pathogenic variant.
case_images: fgene-15-1522203-g002.jpg
case_images: PMC11747468_01_fgene-15-1522203-g002.jpg
case_images: F2
case_images: Considering that the clinical manifestations of the proband and their family members also are consistent with FSHD characteristics, we conducted D4Z4 repeat length analysis and 4qA variant structure and genetic typing analysis on peripheral blood samples from the proband (III3, Figure 2), his maternal grandmother (I2, Figure 2), mother (II2, Figure 2), aunt (II5, Figure 2), uncle (II3, Figure 2) and cousin (III4, Figure 2). The results showed abnormal copy numbers of D4Z4 repeat units in the 4q35 subtelomeric region of 4qA in the proband, his maternal grandmother, mother, aunt, and cousin, while the uncle showed no abnormalities in the copy numbers of D4Z4 repeat units in the 4q35 subtelomeric region of 4qA (Table 1; Supplementary Figure 2). Table 1). These results together with their clinical picture confirmed that the proband, his maternal grandmother, mother, aunt, and cousin were patients with FSHD1 (Figure 2). Overall, the proband and his cousin simultaneously suffer from FSHD1 and BMD (Figure 2), which is extremely rare.