Arterial Dissection With Lentiginosis

Arterial dissection occurs when blood enters a vessel wall through an intimal tear and a false lumen is formed within the media. The arteries most commonly affected by dissection are the aorta, renal artery, and extracranial internal carotid artery, in that order of frequency. A genetic predisposition to arterial dissection is supported by its familial occurrence (see 147820; 607086; 122455) and its association with various heritable disorders of connective tissue, particularly the Marfan syndrome (154700).

Among approximately 240 patients with spontaneous cervical artery dissections seen in a 22-year period at the Mayo Clinic, Schievink et al. (1995) found 8 with a documented family history of arterial dissection. Two of these patients and their families represented instances of arterial dissection occurring at an early age and in association with multiple lentigines. Since the arterial media and melanocytes are derived from neural crest cells, Schievink et al. (1995) suggested that a neural crest defect may be the underlying abnormality in these families. The familial syndrome of arterial dissections with lentiginosis may represent an autosomal recessive disorder since 2 brothers were affected in 1 family and a brother and sister in another, the latter sibs being the progeny of parents related as half third cousins. In 1 family, a brother died suddenly of aortic dissection with rupture of the ascending aorta into the pericardium. Extensive cystic medial necrosis of the aorta was noted. His brother had surgical repair of aortic coarctation just distal to the left subclavian artery at the age of 19 years. At the age of 33 years, he suffered a left parietal lobe infarct, and stenosis due to dissection in the left internal carotid artery was demonstrated by cerebral angiography. Both brothers had numerous hyperpigmented skin lesions, mainly affecting the skin of the extremities, which were demonstrated to represent lentigines. They were of uniform size (approximately 3 mm in diameter) and dark brown to black. Some were present on the trunk and they were also found on the palms and soles. The face and mucous membranes were not involved. The skin lesions developed around the age of 2 years and increased markedly in number during adolescence. The other family was ascertained through a 24-year-old woman who, shortly after a downhill skiing accident, suffered dissection of the left cervical vertebral artery with resulting right hemiparesis and left Horner syndrome (143000). Six and one-half years later, 6 weeks postpartum, she had a sudden right occipital headache while breastfeeding. At the age of 25 years, 1 of her brothers developed a severe headache followed by right hemiparesis. There was no history of preceding trauma. Angiography revealed an area of smooth stenosis of the left extracranial internal carotid artery consistent with dissection. Both the brother and the sister had multiple skin lesions on the trunk and extremities, especially the lower legs. None of these patients had cafe-au-lait spots, ocular hypertelorism or deafness, and all were of normal stature.

The father in the second family reported by Schievink et al. (1995) had developed left hemiparesis at the age of 43 years and died suddenly 2 years later. Medical records were not available. He had no hyperpigmented skin lesions.

Lentigines are distinguished from freckles (ephelides) by their darker color, their presence in areas not exposed to the sun, the fact that they do not darken appreciably or increase in number during exposure to sun, and their relative uncommonness in red-haired and fair-skinned people. Histologically, lentigines have an increased number of melanocytes at the dermoepidermal junction and elongation of the rete ridges, whereas freckles have a normal or slightly decreased number of melanocytes and no elongation of the rete ridges. Lentiginosis is a component of Carney complex (160980) and of the LEOPARD syndrome (151100), but the other features of those syndromes indicate their distinctness from the new one described by Schievink et al. (1995). In the arterial segments available for study in both families, cystic medial necrosis was detected by microscopic examination.