PMC9033252_01
(A) Abnormal facial features (a closed anterior fontanelle, prominent temporal parts, long eyelashes, sparse hair, upturned nostrils, a sharp beak-like mouth, low-set ears, a short neck, and white skin). (B) Wrist joint seam showing significant stenosis. (C) Spine X-ray: slight scoliosis of the spine and slightly narrow vertebral ends of ribs. (D) Spine X-ray: the spine showed slight kyphosis at the junction of the thoracolumbar segment, had short anterior and posterior diameters of some thoracolumbar vertebra, and there was anterior breakage of the vertebral body. (E) Spine X-ray: irregular acetabulum and lower edge of iliac bone. (F) Brain MRI: poor white matter development. (G) Brain MRI: smaller frontal lobe and thinner corpus callosum.
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F1
She had a closed anterior fontanelle, prominent temporal parts, long eyelashes, sparse hair, upturned nostrils, a sharp beak-like mouth, low-set ears, a short neck, and white skin (Figure 1A). The external genitalia was childish, and the wrist joint seam had significant stenosis (Figure 1B). The X-ray of the spine indicated slight scoliosis (Figure 1C). The shape of the vertebral ends of the ribs was slightly narrow and that of the lateral ends was slightly wide (Figure 1D). The shape of the acetabulum and lower edge of the iliac bone was irregular, and the shape of the femoral neck was thin (Figure 1E). B-ultrasound. Brain MRI showed less white matter, smaller frontal lobes, and a thinner corpus callosum (Figures 1F,G).
PMC9033252_02
(A) Abnormal facial features (thick arched eyebrows, a flat nose, swollen eyelids, exophthalmos, epicanthus, low-set ears, and a short neck). (B) Obvious gingival hyperplasia. (C) Anteroposterior chest X-ray: small chest shape, short floating ribs, and irregular bilateral proximal humerus. (D) Pelvis anteroposterior X-ray: sharp and deep bilateral sciatic incisions; small and shallow bilateral acetabulums. (E) Brain MRI: small bilateral frontotemporal lobes, wide extracerebral space, and less white matter. (F) Brain MRI: thinner corpus callosum.
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F2
He had thick arched eyebrows, a flat nose, swollen eyelids, exophthalmos, epicanthus, obvious gingival hyperplasia, low-set ears, a short neck, pectus carinatum, short fingers, and stiff joints (Figures 2A-4B). The bilateral proximal humeri were irregular in shape (Figure 2C). X-ray of the pelvis anteroposterior showed deep cusp of large sciatic notch on both sides, small and shallow shape of the acetabulum on both sides, and lateral position of the bilateral femoral heads (Figure 2D). Cranial MRI showed less white matter, smaller bilateral frontotemporal lobe, thinner corpus callosum, and delayed myelination (Figures 2E,F).
Sanger sequencing chromatograms of the GNPTAB gene variants in case 1. (A) Heterozygous c.1284+1G>T variant inherited from the mother in the GNPTAB gene of the patient. (B) Heterozygous c.1364C>T variant inherited from the father in the GNPTAB gene of the patient.
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F3
He had thick arched eyebrows, a flat nose, swollen eyelids, exophthalmos, epicanthus, obvious gingival hyperplasia, low-set ears, a short neck, pectus carinatum, short fingers, and stiff joints (Figures 2A-4B).
Next-generation sequencing of the GNPTAB gene variants in case 2. (A) Heterozygous c.1284+1G>T and c.483delT variants in the GNPTAB gene of the patient. (B) Heterozygous c.1284+1G>T variant in the GNPTAB gene of the mother. (C) No pathogenic variant was detected in the GNPTAB gene of the father.
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F4
He had thick arched eyebrows, a flat nose, swollen eyelids, exophthalmos, epicanthus, obvious gingival hyperplasia, low-set ears, a short neck, pectus carinatum, short fingers, and stiff joints (Figures 2A-4B).