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. 2018 Oct 29;21(1):47-52.
doi: 10.2478/bjmg-2018-0009. eCollection 2018 Jun.

Clinical Variability in Two Macedonian Families with Arterial Tortuosity Syndrome

M Kocova  1 , R Kacarska  1 , K Kuzevska-Maneva  1 , S Prijic  2 , M Lazareska  3 , C Dordoni  4 , M Ritelli  4 , M Colombi  4
Affiliations

Clinical Variability in Two Macedonian Families with Arterial Tortuosity Syndrome

M Kocova et al. Balkan J Med Genet. .

Abstract

Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disorder caused by mutations in the solute carrier family 2 member 10 (SLC2A10) gene encoding a glucose/ascorbic acid transporter. The clinical features of ATS are mild-to-severe tortuosity of the large and medium arteries throughout the body, accompanied by dysmorphisms and joint laxity. Vascular changes in different parts of the body lead to stenosis and/or aneurysms requiring difficult surgical procedures. Here we present two new patients with ATS from two unrelated families. Patient 1 presented at 10 years of age with headache and typical physical appearance, delicate skeleton, large visible pulsation of the carotid arteries in the neck, and joint laxity. On computed tomography (CT) angiography she had severe tortuosity of the aortal branches and cerebral arteries, but no significant tortuosity of the pulmonary arteries. Two cousins of the girl carried the same homozygous c.254T>C, p.(Leu85Pro) mutation in SLC2A10, however, they additionally had a severe involvement of the pulmonary vessels. Patient 2 was a 9-year-old girl diagnosed with severe tortuosity and stenosis of the pulmonary arteries and progressive myocardiopathy. Her physical appearance was very similar to Patient 1, except that she also had growth retardation. After long-term follow-up by cardiologists, she underwent cardiac surgery abroad, with an unfavorable outcome. Homozygosity for the c.685C>T, p.(Arg229*) mutation in the SLC2A10 gene was detected. Consanguinity was disclosed within both families. Our findings confirm the intrafamilial phenotype variability of ATS. A novel finding is the severe tortuosity of cerebral arteries causing migraine that has not been described before in a child with ATS.

Keywords: Arterial tortuosity syndrome (ATS); Cerebral artery; Consanguinity; Phenotype variability; SLC2A10 gene mutation.

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Figures

Figure 1
Figure 1
Color-coded volume rendering of the brain and neck CT-angiography of P1 with marked tortuosity of the cerebral arteries (black arrows) shown at different cross-sectional levels (A and B) and vertebral arteries (white arrows) shown in sagittal sections (C and D).
Figure 2
Figure 2
Computed tomography angiography of the aortic arch of P1 (A-D). Right subclavian artery (RSA) and right common carotid artery (RCCA) emerge from a right innominate artery, which is the first aortic arch branch (black arrows); left common carotid artery (LCCA) (marked with an asterisk) is the second and left subclavian artery (LSA) is the third aortic arch branch.
Figure 3
Figure 3
Molecular characterization. Sequencing of SLC2A10 exons and splice junctions revealed the following: P1 was homozygous for the c.254T>C, p.(Leu85Pro) missense mutation and P2 was homozygous for the recurrent c.685C>T, p.(Arg229*) nonsense mutation.
Figure 4
Figure 4
Family pedigree of P1. Children affected by ATS are shown in black, P1 is identified by an arrow.
See this image and copyright information in PMC

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