Chapter 37 - Neurologic manifestations of inherited disorders of connective tissue

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Abstract

Inherited disorders of connective tissue are single gene disorders affecting structure or function of the connective tissue. Neurological manifestations are classic and potentially severe complications of many such disorders. The most common neurological manifestations are cerebrovascular. Ischemic stroke is a classic complication of vascular Ehlers–Danlos syndrome (type IV), homocystinuria, and arterial tortuosity syndrome, and may occasionally be seen in Marfan syndrome and pseudoxanthoma elasticum with distinct underlying mechanisms for each disease. Vascular Ehlers–Danlos syndrome can also lead to cervical artery dissection (with or without ischemic stroke), carotid-cavernous fistula, intracranial dissections and aneurysms potentially causing subarachnoid or intracerebral hemorrhage, and arterial rupture. Other neurological manifestations include nerve root compression and intracranial hypotension due to dural ectasia in Marfan and Loeys–Dietz syndrome, spinal cord compression in osteogenesis imperfecta, and mucopolysaccharidosis type I and VI, carpal tunnel syndrome in mucopolysaccharidosis type I, II, and VI. Impaired mental development can be observed in homocystinuria, mucopolysaccharidosis type II, and the severe form of mucopolysaccharidosis type I. For the neurologist, being aware of these complications and of the diagnostic criteria for inherited connective tissue disorders is important since neurological complications can be the first manifestation of the disease and because caution may be warranted for the management of these patients.

Introduction

Inherited disorders of connective tissue are monogenic diseases that affect the structure or function of the connective tissue. While these disorders are transmitted within families according to a Mendelian inheritance pattern, de novo mutations are common and a substantial proportion of patients do not have any family history of the disease. Although neurologic manifestations are often not part of the major diagnostic criteria, they represent classic and potentially severe complications of many inherited connective tissue disorders. For the neurologist, being aware of the main characteristics and diagnostic criteria of these disorders is important for two reasons: (1) in some cases neurologic complications can be the first manifestation of the disease, and (2) special caution may be required for the management of these patients, especially with regards to invasive exams or procedures and antithrombotic therapy. In the first part of this chapter we describe the most common neurologic manifestations of inherited disorders of connective tissue in adults. The second part reviews the main diagnostic and therapeutic implications of these disorders for the practicing neurologist.

Section snippets

Neurologic manifestations of the most common inherited disorders of connective tissue

Inherited disorders of connective tissue leading to neurologic complications are summarized in Table 37.1. The majority of neurologic manifestations are cerebrovascular, mostly due to alterations in the vascular connective tissue. Other neurologic manifestations are mostly secondary to osteoarticular complications.

Conclusions

For the neurologist, being aware of heritable connective tissue disorders and their neurologic complications is particularly important in the following situations:

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