RSS-Feed abonnieren
DOI: 10.1055/s-0044-1786773
Holoprosencephaly: The Disease and Its Related Disabilities
Abstract
Holoprosencephaly (HPE), the most prevalent developmental anomaly affecting the forebrain in humans, occurs in approximately 1 in 16,000 liveborn neonates, with an incidence reaching 1 in 250 in conceptuses. This condition is distributed worldwide. HPE is etiologically heterogeneous, and its pathogenesis is variable. Environmental, teratogenic, genetic, or metabolic factors can contribute to the development of HPE. Notably, maternal insulin-dependent diabetes mellitus and maternal alcoholism are among the primary causative factors. HPE may be linked to various well-defined multiple malformation syndromes characterized by a normal karyotype, such as Smith–Lemli–Opitz's, Pallister–Hall's, or velocardiofacial syndrome. Alternatively, it can be associated with chromosomal abnormalities. (i.e., Patau's syndrome and, less frequently, Edwards' syndrome or Down's syndrome). The major genes implicated in HPE are SHH, ZIC2, SIX3, and TGIF. The range of HPE is extensive, covering diverse neuropathological phenotypes of varying severity. Three classical types of HPE can be distinguished in increasing order of severity: lobar HPE, characterized by separated right and left ventricles with some continuity across the frontal cortex; semilobar HPE, featuring a partial separation; and the most severe form, alobar HPE, where there is a single brain ventricle and the absence of an interhemispheric fissure. Additionally, there are other variations of HPE, ranging in severity, including the less severe interhemispheric median HPE (also known as middle interhemispheric variant). The phenotypic spectrum of HPE is highly extensive, encompassing severe cerebral malformations to microforms. Children with HPE often encounter numerous medical challenges; among them neurological disorders, craniofacial malformations, endocrine disorders, oral and motor dysfunction, and dysfunction of the autonomic nervous system. Neurologic problems, such as cerebral palsy and seizures, are common. The diagnosis of HPE is typically made prenatally, relying primarily on ultrasound and magnetic resonance imaging examinations. The prognosis for individuals with HPE is largely dependent on its underlying causes. Those with cytogenetic abnormalities, in particular, face a significantly poorer prognosis, with only 2% surviving beyond 1 year.
* These authors have equally contributed to this article.
Publikationsverlauf
Eingereicht: 11. Dezember 2023
Angenommen: 04. April 2024
Artikel online veröffentlicht:
11. Mai 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Kauvar EF, Solomon BD, Curry CJ. et al. Holoprosencephaly and agnathia spectrum: presentation of two new patients and review of the literature. Am J Med Genet C Semin Med Genet 2010; 154C (01) 158-169
- 2 Pavone P, Rizzo R, Conti I. et al. Primary headaches in children: clinical findings on the association with other conditions. Int J Immunopathol Pharmacol 2012; 25 (04) 1083-1091
- 3 Croen LA, Shaw GM, Lammer EJ. Holoprosencephaly: epidemiologic and clinical characteristics of a California population. Am J Med Genet 1996; 64 (03) 465-472
- 4 Pavone P, Praticò AD, Falsaperla R. et al. Congenital generalized hypertrichosis: the skin as a clue to complex malformation syndromes. Ital J Pediatr 2015; 41: 55
- 5 Blaas HG, Eriksson AG, Salvesen KA. et al. Brains and faces in holoprosencephaly: pre- and postnatal description of 30 cases. Ultrasound Obstet Gynecol 2002; 19 (01) 24-38
- 6 Praticò AD, Pavone P, Scuderi MG. et al. Symptomatic hypocalcemia in an epileptic child treated with valproic acid plus lamotrigine: a case report. Cases J 2009; 2: 7394
- 7 Cohen Jr MM. Perspectives on holoprosencephaly: part I. Epidemiology, genetics, and syndromology. Teratology 1989; 40 (03) 211-235
- 8 Pavone P, Falsaperla R, Ruggieri M. et al. Clinical course of N-methyl-D-aspartate receptor encephalitis and the effectiveness of cyclophosphamide treatment. J Pediatr Neurol 2017; 15 (02) 84-89
- 9 Cohen Jr MM. Perspectives on holoprosencephaly: part III. Spectra, distinctions, continuities, and discontinuities. Am J Med Genet 1989; 34 (02) 271-288
- 10 Pavone P, Nigro F, Falsaperla R. et al. Hemihydranencephaly: living with half brain dysfunction. Ital J Pediatr 2013; 39: 3
- 11 Roach E, Demyer W, Conneally PM, Palmer C, Merritt AD. Holoprosencephaly: birth data, benetic and demographic analyses of 30 families. Birth Defects Orig Artic Ser 1975; 11 (02) 294-313
- 12 Falsaperla R, Perciavalle V, Pavone P. et al. Unilateral eye blinking arising from the ictal ipsilateral occipital area. Clin EEG Neurosci 2016; 47 (03) 243-246
- 13 Matsunaga E, Shiota K. Holoprosencephaly in human embryos: epidemiologic studies of 150 cases. Teratology 1977; 16 (03) 261-272
- 14 Pavone P, Falsaperla R, Ruggieri M, Praticò AD, Pavone L. West syndrome treatment: new roads for an old syndrome. Front Neurol 2013; 4: 113
- 15 Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V. Holoprosencephaly. Orphanet J Rare Dis 2007; 2: 8
- 16 Ruggieri M, Polizzi A, Marceca GP, Catanzaro S, Praticò AD, Di Rocco C. Introduction to phacomatoses (neurocutaneous disorders) in childhood. Childs Nerv Syst 2020; 36 (10) 2229-2268
- 17 Barr Jr M, Hanson JW, Currey K. et al. Holoprosencephaly in infants of diabetic mothers. J Pediatr 1983; 102 (04) 565-568
- 18 Incorpora G, Pavone P, Castellano-Chiodo D, Praticò AD, Ruggieri M, Pavone L. Gelastic seizures due to hypothalamic hamartoma: rapid resolution after endoscopic tumor disconnection. Neurocase 2013; 19 (05) 458-461
- 19 Croen LA, Shaw GM, Lammer EJ. Risk factors for cytogenetically normal holoprosencephaly in California: a population-based case-control study. Am J Med Genet 2000; 90 (04) 320-325
- 20 Vitaliti G, Praticò AD, Cimino C. et al. Hepatitis B vaccine in celiac disease: yesterday, today and tomorrow. World J Gastroenterol 2013; 19 (06) 838-845
- 21 Repetto M, Maziere JC, Citadelle D. et al. Teratogenic effect of the cholesterol synthesis inhibitor AY 9944 on rat embryos in vitro. Teratology 1990; 42 (06) 611-618
- 22 Leonardi S, Praticò AD, Lionetti E, Spina M, Vitaliti G, La Rosa M. Intramuscular vs intradermal route for hepatitis B booster vaccine in celiac children. World J Gastroenterol 2012; 18 (40) 5729-5733
- 23 Frenkel LD, Gaur S, Tsolia M, Scudder R, Howell R, Kesarwala H. Cytomegalovirus infection in children with AIDS. Rev Infect Dis 1990; 12 (Suppl. 07) S820-S826
- 24 Vitaliti G, Cimino C, Coco A, Praticò AD, Lionetti E. The immunopathogenesis of cow's milk protein allergy (CMPA). Ital J Pediatr 2012; 38: 35 Erratum in: Ital J Pediatr 2014;39:82
- 25 Byrne PJ, Silver MM, Gilbert JM, Cadera W, Tanswell AK. Cyclopia and congenital cytomegalovirus infection. Am J Med Genet 1987; 28 (01) 61-65
- 26 Palano GM, Praticò AD, Praticò ER. et al. Accidental ethyl alcohol intoxication in a 30-day-old infant. Clinical findings and neurological follow-up. Minerva Pediatr 2007; 59 (03) 275-279
- 27 Kelley RL, Roessler E, Hennekam RC. et al. Holoprosencephaly in RSH/Smith-Lemli-Opitz syndrome: does abnormal cholesterol metabolism affect the function of sonic hedgehog?. Am J Med Genet 1996; 66 (04) 478-484
- 28 Fiumara A, Lanzafame G, Arena A. et al. COVID-19 pandemic outbreak and its psychological impact on patients with rare lysosomal diseases. J Clin Med 2020; 9 (09) 2716
- 29 Hall JG, Pallister PD, Clarren SK. et al. Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and postaxial polydactyly–a new syndrome? Part I: clinical, causal, and pathogenetic considerations. Am J Med Genet 1980; 7 (01) 47-74
- 30 Praticò AD, Leonardi S. Immunotherapy for food allergies: a myth or a reality?. Immunotherapy 2015; 7 (02) 147-161
- 31 Wraith JE, Super M, Watson GH, Phillips M. Velo-cardio-facial syndrome presenting as holoprosencephaly. Clin Genet 1985; 27 (04) 408-410
- 32 Pratico AD, Salafia S, Barone P, La Rosa M, Leonardi S. Type II autoimmune hepatitis and small duct sclerosing cholangitis in a seven years old child: an overlap syndrome?. Hepat Mon 2013; 13 (12) e14452
- 33 Dubourg C, Lazaro L, Pasquier L. et al. Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations. Hum Mutat 2004; 24 (01) 43-51
- 34 Praticò AD, Ruggieri M. COVID-19 vaccination for children: may be necessary for the full eradication of the disease. Pediatr Res 2021; 90 (06) 1102-1103
- 35 Bendavid C, Dubourg C, Gicquel I. et al. Molecular evaluation of foetuses with holoprosencephaly shows high incidence of microdeletions in the HPE genes. Hum Genet 2006; 119 (1-2): 1-8
- 36 Praticò AD, Polizzi A, Salafia R. et al. Megalencephaly capillary malformation syndrome. J Pediatr Neurol 2018; 16 (05) 328-337
- 37 Lazaro L, Dubourg C, Pasquier L. et al. Phenotypic and molecular variability of the holoprosencephalic spectrum. Am J Med Genet A 2004; 129A (01) 21-24
- 38 Praticò AD, Mistrello G, La Rosa M. et al. Immunotherapy: a new horizon for egg allergy?. Expert Rev Clin Immunol 2014; 10 (05) 677-686
- 39 Demyer W, Zeman W. Alobar holoprosencephaly (arhinencephaly) with median cleft lip and palate: clinical, electroencephalographic and nosologic considerations. Confin Neurol 1963; 23: 1-36
- 40 La Mendola F, Fatuzzo V, Smilari P. et al. Multiseptate gallbladder in a child: a possible cause of poor growth?. J Pediatr Gastroenterol Nutr 2019; 68 (01) e13
- 41 Barkovich AJ, Quint DJ. Middle interhemispheric fusion: an unusual variant of holoprosencephaly. AJNR Am J Neuroradiol 1993; 14 (02) 431-440
- 42 Praticò AD. COVID-19 pandemic for pediatric health care: disadvantages and opportunities. Pediatr Res 2021; 89 (04) 709-710
- 43 Garrido Márquez I, Fernández Navarro L, Moya Sánchez E. The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI. Radiología (Engl Ed) 2022; 64 (04) 375-378
- 44 Polizzi A, Pavone P, Ciancio E, La Rosa C, Sorge G, Ruggieri M. Hypertrichosis cubiti (hairy elbow syndrome): a clue to a malformation syndrome. J Pediatr Endocrinol Metab 2005; 18 (10) 1019-1025
- 45 McCabe MJ, Gaston-Massuet C, Tziaferi V. et al. Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction. J Clin Endocrinol Metab 2011; 96 (10) E1709-E1718
- 46 Pavone P, Polizzi A, Marino SD. et al. West syndrome: a comprehensive review. Neurol Sci 2020; 41 (12) 3547-3562
- 47 Hahn JS, Plawner LL. Evaluation and management of children with holoprosencephaly. Pediatr Neurol 2004; 31 (02) 79-88
- 48 Ruggieri M, Praticò AD, Serra A. et al. Early history of neurofibromatosis type 2 and related forms: earliest descriptions of acoustic neuromas, medical curiosities, misconceptions, landmarks and the pioneers behind the eponyms. Childs Nerv Syst 2017; 33 (04) 549-560
- 49 Geng X, Oliver G. Pathogenesis of holoprosencephaly. J Clin Invest 2009; 119 (06) 1403-1413
- 50 Polizzi A, Coghill S, McShane MA, Squier W. Acute ataxia complicating Langherans cell histiocytosis. Arch Dis Child 2002; 86 (02) 130-131
- 51 Jeong Y, El-Jaick K, Roessler E, Muenke M, Epstein DJ. A functional screen for sonic hedgehog regulatory elements across a 1 Mb interval identifies long-range ventral forebrain enhancers. Development 2006; 133 (04) 761-772
- 52 Nicita F, Ruggieri M, Polizzi A. et al. Seizures and epilepsy in Sotos syndrome: analysis of 19 Caucasian patients with long-term follow-up. Epilepsia 2012; 53 (06) e102-e105
- 53 Marciniak C, McAllister P, Walker H. et al; International AbobotulinumtoxinA Adult Upper Limb Spasticity Study Group. Efficacy and safety of abobotulinumtoxinA (Dysport) for the treatment of hemiparesis in adults with upper limb spasticity previously treated with botulinum toxin: subanalysis from a phase 3 randomized controlled trial. PM R 2017; 9 (12) 1181-1190
- 54 Vecchio M, Gracies JM, Panza F. et al. Change in coefficient of fatigability following rapid, repetitive movement training in post-stroke spastic paresis: a prospective open-label observational study. J Stroke Cerebrovasc Dis 2017; 26 (11) 2536-2540
- 55 Gracies JM, Jech R, Valkovic P. et al. When can maximal efficacy occur with repeat botulinum toxin injection in upper limb spastic paresis?. Brain Commun 2020; 3 (01) fcaa201
- 56 Chiaramonte R, Pavone P, Vecchio M. Speech rehabilitation in dysarthria after stroke: a systematic review of the studies. Eur J Phys Rehabil Med 2020; 56 (05) 547-562
- 57 Chiaramonte R, Vecchio M. Dysarthria and stroke. The effectiveness of speech rehabilitation. A systematic review and meta-analysis of the studies. Eur J Phys Rehabil Med 2021; 57 (01) 24-43
- 58 Chiaramonte R, Vecchio M. A systematic review of measures of dysarthria severity in stroke patients. PM R 2021; 13 (03) 314-324
- 59 Muenke M, Cohen Jr MM. Genetic approaches to understanding brain development: holoprosencephaly as a model. Ment Retard Dev Disabil Res Rev 2000; 6 (01) 15-21
- 60 Ruggieri M, Polizzi A. From Aldrovandi's “Homuncio” (1592) to Buffon's girl (1749) and the “Wart Man” of Tilesius (1793): antique illustrations of mosaicism in neurofibromatosis?. J Med Genet 2003; 40 (03) 227-232
- 61 Winter TC, Kennedy AM, Woodward PJ. Holoprosencephaly: a survey of the entity, with embryology and fetal imaging. Radiographics 2015; 35 (01) 275-290
- 62 Matricardi S, Spalice A, Salpietro V. et al. Epilepsy in the setting of full trisomy 18: a multicenter study on 18 affected children with and without structural brain abnormalities. Am J Med Genet C Semin Med Genet 2016; 172 (03) 288-295
- 63 Volpe P, Campobasso G, De Robertis V, Rembouskos G. Disorders of prosencephalic development. Prenat Diagn 2009; 29 (04) 340-354
- 64 Sorge G, Ruggieri M, Polizzi A, Scuderi A, Di Pietro M. SHORT syndrome: a new case with probable autosomal dominant inheritance. Am J Med Genet 1996; 61 (02) 178-181
- 65 Monteagudo A. Society for Maternal-Fetal Medicine (SMFM). Holoprosencephaly. Am J Obstet Gynecol 2020; 223 (06) B13-B16
- 66 Ruggieri M, Tigano G, Mazzone D, Tiné A, Pavone L. Involvement of the white matter in hypomelanosis of Ito (incontinentia pigmenti achromiens). Neurology 1996; 46 (02) 485-492
- 67 Salpietro V, Phadke R, Saggar A. et al. Zellweger syndrome and secondary mitochondrial myopathy. Eur J Pediatr 2015; 174 (04) 557-563
- 68 O'Connor KC, Lopez-Amaya C, Gagne D. et al. Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis. J Neuroimmunol 2010; 223 (1-2): 92-99
- 69 Salpietro V, Polizzi A, Di Rosa G. et al. Adrenal disorders and the paediatric brain: pathophysiological considerations and clinical implications. Int J Endocrinol 2014; 2014: 282489
- 70 Ruggieri M, Polizzi A. Segmental neurofibromatosis. J Neurosurg 2000; 93 (03) 530-532
- 71 Salpietro V, Ruggieri M, Sancetta F. et al. New insights on the relationship between pseudotumor cerebri and secondary hyperaldosteronism in children. J Hypertens 2012; 30 (03) 629-630
- 72 Falsaperla R, Praticò AD, Ruggieri M. et al. Congenital muscular dystrophy: from muscle to brain. Ital J Pediatr 2016; 42 (01) 78