Recognition and Diagnosis of Neuro-Ichthyotic Syndromes

Abstract

The combination of neurologic disease and ichthyosis defines a heterogeneous group of rare inherited disorders that present in infancy through early adulthood. Although affected patients share the cutaneous feature of ichthyosis, there is variability in the nature and severity of neurologic disease. Impaired cognition, spasticity, sensorineural deafness, visual impairment, and/or seizures are the primary neurologic findings. Most of these disorders are caused by genetic defects in lipid metabolism, glycoprotein synthesis, or intracellular vesicle trafficking. The clinical features of some of the neuro-ichthyoses are distinct enough to allow their clinical recognition, but confirmatory biochemical or genetic tests are necessary for accurate diagnosis. Treatment of the ichthyosis is largely symptomatic, and except for Refsum's disease, there are no effective pathogenesis-based therapies for the neurologic disease.

Keywords

ichthyosis - lipids - mutation - skin - myelin

• References

• 1 Rizzo WB. Sjögren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab 2007; 90 (1) 1-9
• 2 Willemsen MA, Van Der Graaf M, Van Der Knaap MS , et al. MR imaging and proton MR spectroscopic studies in Sjögren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol 2004; 25 (4) 649-657
• 3 Rizzo WB, Carney G. Sjögren-Larsson syndrome: diversity of mutations and polymorphisms in the fatty aldehyde dehydrogenase gene (ALDH3A2). Hum Mutat 2005; 26 (1) 1-10
• 4 Rizzo WB, S'Aulis D, Jennings MA, Crumrine DA, Williams ML, Elias PM. Ichthyosis in Sjögren-Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion. Arch Dermatol Res 2010; 302 (6) 443-451
• 5 Demerjian M, Crumrine DA, Milstone LM, Williams ML, Elias PM. Barrier dysfunction and pathogenesis of neutral lipid storage disease with ichthyosis (Chanarin-Dorfman syndrome). J Invest Dermatol 2006; 126 (9) 2032-2038
• 6 Lefèvre C, Jobard F, Caux F , et al. Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioest-erase subfamily, in Chanarin - Dorfman syndrome. Am J Hum Genet 2001; 69 (5) 1002-1012
• 7 Uchida Y, Cho Y, Moradian S , et al. Neutral lipid storage leads to acylceramide deficiency, likely contributing to the pathogenesis of Dorfman-Chanarin syndrome. J Invest Dermatol 2010; 130 (10) 2497-2499
• 8 van den Brink DM, Wanders RJ. Phytanic acid: production from phytol, its breakdown and role in human disease. Cell Mol Life Sci 2006; 63 (15) 1752-1765
• 9 Wanders RJ, Jakobs C, Skjeldal OH. Refsum disease. In: The Metabolic & Molecular Bases of Inherited Disease. New York: McGraw-Hill; 2001: 3303-3321
• 10 Perera NJ, Lewis B, Tran H, Fietz M, Sullivan DR. Refsum's disease-use of the intestinal lipase inhibitor, Orlistat, as a novel therapeutic approach to a complex disorder. J Obes 2011; 2011
• 11 Stone DL, Carey WF, Christodoulou J , et al. Type 2 Gaucher disease: the collodion baby phenotype revisited. Arch Dis Child Fetal Neonatal Ed 2000; 82 (2) F163-F166
• 12 Stone DL, Tayebi N, Orvisky E, Stubblefield B, Madike V, Sidransky E. Glucocerebrosidase gene mutations in patients with type 2 Gaucher disease. Hum Mutat 2000; 15 (2) 181-188
• 13 Aldahmesh MA, Mohamed JY, Alkuraya HS , et al. Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability, and spastic quadriplegia. Am J Hum Genet 2011; 89 (6) 745-750
• 14 Vasireddy V, Uchida Y, Salem Jr N , et al. Loss of functional ELOVL4 depletes very long-chain fatty acids (> or =C28) and the unique ω-O-acylceramides in skin leading to neonatal death. Hum Mol Genet 2007; 16 (5) 471-482
• 15 Cosma MP, Pepe S, Annunziata I , et al. The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases. Cell 2003; 113 (4) 445-456
• 16 Dierks T, Dickmanns A, Preusser-Kunze A , et al. Molecular basis for multiple sulfatase deficiency and mechanism for formylglycine generation of the human formylglycine-generating enzyme. Cell 2005; 121 (4) 541-552
• 17 Schlotawa L, Ennemann EC, Radhakrishnan K , et al. SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency. Eur J Hum Genet 2011; 19 (3) 253-261
• 18 Curry CJ, Magenis RE, Brown M , et al. Inherited chondrodysplasia punctata due to a deletion of the terminal short arm of an X chromosome. N Engl J Med 1984; 311 (16) 1010-1015
• 19 Bick DP, Schorderet DF, Price PA , et al. Prenatal diagnosis and investigation of a fetus with chondrodysplasia punctata, ichthyosis, and Kallmann syndrome due to an Xp deletion. Prenat Diagn 1992; 12 (1) 19-29
• 20 Kranz C, Jungeblut C, Denecke J , et al. A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy. Am J Hum Genet 2007; 80 (3) 433-440
• 21 Morava E, Wevers RA, Cantagrel V , et al. A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism. Brain 2010; 133 (11) 3210-3220
• 22 Richard G, Rouan F, Willoughby CE , et al. Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome. Am J Hum Genet 2002; 70 (5) 1341-1348
• 23 Mazereeuw-Hautier J, Bitoun E, Chevrant-Breton J , et al. Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients. Br J Dermatol 2007; 156 (5) 1015-1019
• 24 Terrinoni A, Codispoti A, Serra V , et al. Connexin 26 (GJB2) mutations, causing KID syndrome, are associated with cell death due to calcium gating deregulation. Biochem Biophys Res Commun 2010; 394 (4) 909-914
• 25 Sprecher E, Ishida-Yamamoto A, Mizrahi-Koren M , et al. A mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking, causes a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma. Am J Hum Genet 2005; 77 (2) 242-251
• 26 Fuchs-Telem D, Stewart H, Rapaport D , et al. CEDNIK syndrome results from loss-of-function mutations in SNAP29. Br J Dermatol 2011; 164 (3) 610-616
• 27 Rapaport D, Lugassy Y, Sprecher E, Horowitz M. Loss of SNAP29 impairs endocytic recycling and cell motility. PLoS ONE 2010; 5 (3) e9759
• 28 Montpetit A, Côté S, Brustein E , et al. Disruption of AP1S1, causing a novel neurocutaneous syndrome, perturbs development of the skin and spinal cord. PLoS Genet 2008; 4 (12) e1000296
• 29 Gissen P, Johnson CA, Morgan NV , et al. Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome. Nat Genet 2004; 36 (4) 400-404
• 30 Choi HJ, Lee MW, Choi JH, Moon KC, Koh JK. Ichthyosis associated with ARC syndrome: ARC syndrome is one of the differential diagnoses of ichthyosis. Pediatr Dermatol 2005; 22 (6) 539-542
• 31 Abu-Sa'da O, Barbar M, Al-Harbi N, Taha D. Arthrogryposis, renal tubular acidosis and cholestasis (ARC) syndrome: two new cases and review. Clin Dysmorphol 2005; 14 (4) 191-196
• 32 Faghri S, Tamura D, Kraemer KH, Digiovanna JJ. Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations. J Med Genet 2008; 45 (10) 609-621
• 33 Stefanini M, Botta E, Lanzafame M, Orioli D. Trichothiodystrophy: from basic mechanisms to clinical implications. DNA Repair (Amst) 2010; 9 (1) 2-10
• 34 Elias PM, William ML, Crumrine D, Schmuth M. Ichthyosis: clinical, biochemical, pathogenic and diagnostic assessment. In: Current Problems in Dermatology. Vol. 39. Basel: Karger; 2010