Neurofibromatosis Cardinal features: multiple pigmented birthmarks on skin (“café-au-lait” spots), multiple neurofibromas. Two forms: neurofibromatosis type 1 (NF-1; von Recklinghausen disease, peripheral neurofibromatosis), neurofibromatosis type 2 (NF-2; central neurofibromatosis, bilateral…
Mitochondrial Diseases with Mutations of Nuclear DNA Most autosomal recessive, lack ragged red fibers (RRFs). Onset: infancy or childhood. Can be classified biochemically (Table 99.1). Selected disorders described below. Table…
Leber Hereditary Optic Neuropathy Loss of central vision. Maternal inheritance; point mutation in mtDNA. 60% to 90% of patients are men. Clinical Features Onset: adolescence or early adult years; progressive…
Mitochondrial Encephalomyopathies: Diseases of Mitochondrial DNA Two genomes control mitochondria: mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Diseases caused by nDNA mutations: Mendelian inheritance (see Chapter 99). Diseases caused by…
Differential Diagnosis Useful diagnostic resources include two online databases searchable by physical findings: On-Line Mendelian Inheritance in Man (OMIM, http://www-ncbi-nlm-nih-gov.easyaccess1.lib.cuhk.edu.hk/omim); SimulConsult Neurological Syndromes (http://www.simulconsult.com) Useful clues: inheritance pattern (Table 96.1),…
Diffuse Sclerosis Variant of multiple sclerosis; etiology, pathogenesis unknown. Also known as Schilder disease. Clinical syndrome: leukoencephalopathy (progressive dementia, psychosis, corticospinal signs, loss of vision, brainstem signs); onset usually in…
Cerebral Degenerations of Childhood Canavan Disease (Spongy Degeneration of the Nervous System) Autosomal recessive megalencephaly and neurologic degeneration. Prevalent among Ashkenazi Jews from eastern Europe and among Saudi Arabians. Clinical…
Neurologic Syndromes with Acanthocytes Acanthocytes (“thorny” erythrocytes) seen in three hereditary neurologic syndromes: abetalipoproteinemia, neuroacanthocytosis, McLeod syndrome. Abetalipoproteinemia (Bassen-Kornzweig Syndrome) Autosomal recessive; inability of liver and intestine to secrete apolipoprotein…
Acute Intermittent Porphyria Neurologic manifestations in two classes: acute intermittent porphyria (AIP) and variegate porphyria. Both autosomal dominant, low penetrance. Prevalence worldwide approximately 1:100,000. More common in women than men….
Disorders of Metal Metabolism Hepatolenticular Degeneration (Wilson Disease) Inborn error of copper metabolism; with liver cirrhosis, basal ganglia degeneration. Worldwide prevalence: 30 per 1 million. Pathogenesis and Pathology Autosomal recessive….
