PMC6262175_01
(A) CT minimum intensity projection (MIP) Sagittal (a: right parasagittal plane, b: midsagittal plane, c: left parasagittal plane) and Coronal (d: anterior atlanto-occipital complete fusion, e: lateral masses atlanto-occipital bilateral complete fusion, f: posterior atlanto-occipital partial fusion) CCJ reconstruction. Complete C 1 anterior arch and lateral masses fusion and partial fusion of the posterior arch to the occipital foramen (double-headed arrows). Foramen arcuate (white harrows). Note the "comma" appearance of complete anterior atlanto-occipital fusion (curved harrow) and the smaller odontoid process (arrowhead). (B) CT Coronal (a) and transverse minimum intensity projection (MIP) (b-e) and transverse shaded surface display (SSD) (f) reconstructions of narrowed foramen magnum due to right occipito-condylar hyperplasia (withe arrows). (C) MR transverse T2 (a), T1 (b), FLAIR (c) and coronal FLAIR (d) weighed sequences, show right ventrolateral compression of the lower medulla and upper cervical spinal cord (white arrow) at the level of narrowed foramen magnum due to CCJ complex malformation (black star).
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F1
Arcuate foramen was also observed on the left side (Figure 1A). The atlanto-dental interval (AADI: distance, on the sagittal plane, between the anterior assimilated C1 arch and the odontoid process) (Zong et al.,) appeared increased (10 mm) suggesting an atlanto-axial instability (AAI) (Figure 1A), defined for atlanto-dental interval >3 mm (Gamble and Rinsky,; Ferreira and Botelho,). The odontoid process was smaller (Figure 1A) than normal average (Zong et al.,). The patient is affected as well by a right occipito-condylar hyperplasia, producing narrowing and malformation of both the foramen magnum and the upper cervical spine canal (Figure 1B). This hyperplasia causes the compression and displacement of the right side of the bulbo-medullary junction (Figure 1C).
PMC6262175_02
(A) CT minimum intensity projection (MIP) Sagittal (a: right parasagittal plane, b: midsagittal plane, c: left parasagittal plane) and Coronal (d: anterior atlanto-occipital complete fusion, e: lateral masses atlanto-occipital bilateral complete fusion, f: posterior atlanto-occipital partial fusion) CCJ reconstruction. Complete C 1 anterior arch and lateral masses fusion and partial fusion of the posterior arch to the occipital foramen (double-headed arrows). Foramen arcuate (white harrows). Note the "comma" appearance of complete anterior atlanto-occipital fusion (curved harrow) and the smaller odontoid process (arrowhead). (B) CT Coronal (a) and transverse minimum intensity projection (MIP) (b-e) and transverse shaded surface display (SSD) (f) reconstructions of narrowed foramen magnum due to right occipito-condylar hyperplasia (withe arrows). (C) MR transverse T2 (a), T1 (b), FLAIR (c) and coronal FLAIR (d) weighed sequences, show right ventrolateral compression of the lower medulla and upper cervical spinal cord (white arrow) at the level of narrowed foramen magnum due to CCJ complex malformation (black star).
fgene-09-00549-g0001.jpg
PMC6262175_02_fgene-09-00549-g0001.jpg
F1
Arcuate foramen was also observed on the left side (Figure 1A). The atlanto-dental interval (AADI: distance, on the sagittal plane, between the anterior assimilated C1 arch and the odontoid process) (Zong et al.,) appeared increased (10 mm) suggesting an atlanto-axial instability (AAI) (Figure 1A), defined for atlanto-dental interval >3 mm (Gamble and Rinsky,; Ferreira and Botelho,). The odontoid process was smaller (Figure 1A) than normal average (Zong et al.,). The patient is affected as well by a right occipito-condylar hyperplasia, producing narrowing and malformation of both the foramen magnum and the upper cervical spine canal (Figure 1B). This hyperplasia causes the compression and displacement of the right side of the bulbo-medullary junction (Figure 1C).
(A) Transverse (a-c) and Coronal (d) minimum intensity projection (MIP) CT temporal bone study. Right external auditory canal malformation (a) (white arrow); right chronic otitis media (b) (white star); ankyloses of left ossicular chain (c) (white circle); right widening of facial canal (third segment) (dotted arrow) and partial calcification of left tympanic membrane (arrowhead) (d). (B) MR Coronal T2 (a-c, e), Sagittal T1 (d), and Sagittal T2 (f) weighed sequences whole spine study. The study shows, besides rotoscoliosis (a, b), cervical (C 2-C 3, C 4-C 5) (d, f) and lumbar (L 4-L 5) vertebral fusion (white arrows), and L 5 bilateral sacralisation (e) (white stars) (KFS type II malformation).
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F2
Whole spinal cord MRI study added further information, showing not only rotoscoliosis, but also cervical (C2 - C3, C4 - C5) and lumbar (L4 - L5) vertebral fusion and bilateral L5 sacralisation (Figure 2B).
In the gene view (top), the probe distribution and signal intensity are shown for the index patient (green) and her parents (red and blue), with a green bar indicating the deletion detected with 8 probes. In the UCSC graphic view (middle), a similarly colored bar corresponds to the minimal aberration length, while the flanking grey bars indicate the 5' and 3' breakpoint boundaries. The results of genomic quantification by real-time PCR are schematically represented (bottom). The middle base-pair position of each amplicon along chromosome is surmounted by a square corresponding to the number of detected copies.
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F3
We then carried out array-CGH analysis in the proband and her parents, confirming the presence of a wider de novo heterozygous microdeletion on chromosome 12q13.2-q13.3 (Figure 3).