Journal of Pediatric Neurology 2018; 16(05): 362-368
DOI: 10.1055/s-0038-1667021
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Cerebellotrigeminal Dermal Dysplasia (Gómez-López-Hernández Syndrome)

Federica Sullo
1   Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Andrea D. Praticò
1   Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
2   Maurice Wohl Clinical Neuroscience Institute, King's College London, London, United Kingdom
,
Agata Polizzi
3   Instiute of Neurological Science, National Research Council, Catania, Italy
,
Stefano Catanzaro
1   Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Selene Mantegna
10   Post-graduate School of Pediatrics, Anna Meyer Children's University Hospital, Department of Health Science University of Florence, Florence, Italy
,
Francesco Lacarrubba
4   Dermatology Clinic, University of Catania, Catania, Italy
,
Giuseppe Micali
4   Dermatology Clinic, University of Catania, Catania, Italy
,
Agata Fiumara
5   Unit of Clinical Pediatrics, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Pierluigi Smilari
5   Unit of Clinical Pediatrics, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Filippo Greco
5   Unit of Clinical Pediatrics, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Carmelo Schepis
6   Unit of Dermatology, Oasi Research Institute-IRCCS, Troina, Enna, Italy
,
Concetta Pirrone
7   Section of Psychology, Department of Educational Sciences University of Catania, Catania, Italy
,
Antonio Zanghì
8   Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania, Italy
,
Ignacio Pascual-Castroviejo
9   Servicio de Neurología, Hospital Universitario La Paz, Madrid, España
,
Martino Ruggieri
1   Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
› Author Affiliations
Further Information

Publication History

27 January 2018

17 May 2018

Publication Date:
20 August 2018 (online)

Abstract

Cerebellotrigeminal dermal (CTD) dysplasia is a rare neurocutaneous disorder characterized by a triad of symptoms: bilateral parieto-occipital alopecia, facial anesthesia in the trigeminal area, and rhombencephalosynapsis (RES), confirmed by cranial magnetic resonance imaging. CTD dysplasia is also known as Gómez-López-Hernández syndrome. So far, only 35 cases have been described with varying symptomatology. The etiology remains unknown. Either spontaneous dominant mutations or de novo chromosomal rearrangements have been proposed as possible explanations. In addition to its clinical triad of RES, parietal alopecia, and trigeminal anesthesia, CTD dysplasia is associated with a wide range of phenotypic and neurodevelopmental abnormalities.

Treatment is symptomatic and includes physical rehabilitation, special education, dental care, and ocular protection against self-induced corneal trauma that causes ulcers and, later, corneal opacification. The prognosis is correlated to the mental development, motor handicap, corneal–facial anesthesia, and visual problems. Follow-up on a large number of patients with CTD dysplasia has never been reported and experience is limited to few cases to date. High degree of suspicion in a child presenting with characteristic alopecia and RES has a great importance in diagnosis of this syndrome.

 
  • References

  • 1 OMIM ™. Online Mendelian Inheritance in Man. Baltimore: Johns Hopkins University.2017. Available at: http://ncbi.nlm.nih.gov/omim . Accessed January 12, 2018
  • 2 Muñoz Rojas MV, dos Santos AC, De Pina-Neto JM. Cerebello-trigemino-dermal dysplasia. In: Roach ES, Miller VS. , eds. Neurocutaneous Disorders. Cambridge: Cambridge University Press; 2004: 306-312
  • 3 Brocks D, Irons M, Sadeghi-Najad A, McCauley R, Wheeler P. Gomez-Lopez-Hernandez syndrome: expansion of the phenotype. Am J Med Genet 2000; 94 (05) 405-408
  • 4 Polizzi A, Coghill S, McShane MA, Squier W. Acute ataxia complicating Langerhans cell histiocytosis. Arch Dis Child 2002; 86 (02) 130-131
  • 5 Brancati F, Travaglini L, Zablocka D. , et al; International JSRD Study Group. RPGRIP1L mutations are mainly associated with the cerebello-renal phenotype of Joubert syndrome-related disorders. Clin Genet 2008; 74 (02) 164-170
  • 6 Polizzi A, Pavone P, Iannetti P, Manfré L, Ruggieri M. Septo-optic dysplasia complex: a heterogeneous malformation syndrome. Pediatr Neurol 2006; 34 (01) 66-71
  • 7 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
  • 8 Pavone P, Nigro F, Falsaperla R. , et al. Hemihydranencephaly: living with half brain dysfunction. Ital J Pediatr 2013; 39: 3
  • 9 Ruggieri M, Pavone V, De Luca D, Franzò A, Tiné A, Pavone L. Congenital bone malformations in patients with neurofibromatosis type 1 (Nf1). J Pediatr Orthop 1999; 19 (03) 301-305
  • 10 Salpietro V, Mankad K, Kinali M. , et al. Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: a pilot study. J Pediatr Endocrinol Metab 2014; 27 (1–2): 107-115
  • 11 Ruggieri M, Pavone V, Polizzi A. , et al. Tuberculosis of the ankle in childhood: clinical, roentgenographic and computed tomography findings. Clin Pediatr (Phila) 1997; 36 (09) 529-534
  • 12 Ruggieri M, Huson SM. The neurofibromatoses. An overview. Ital J Neurol Sci 1999; 20 (02) 89-108
  • 13 Ruggieri M, Pavone V, Polizzi A. , et al. Unusual form of recurrent multinucleated giant cell granuloma of the mandible and lower extremities in a patient with neurofibromatosis type 1. Surg Med Pathol Oral Radiol Endod 1999; 87: 67-72
  • 14 Trifiletti RR, Incorpora G, Polizzi A, Cocuzza MD, Bolan EA, Parano E. Aicardi syndrome with multiple tumors: a case report with literature review. Brain Dev 1995; 17 (04) 283-285
  • 15 Ruggieri M, Gabriele AL, Polizzi A. , et al. Natural history of neurofibromatosis type 2 with onset before the age of 1 year. Neurogenetics 2013; 14 (02) 89-98
  • 16 Ruggieri M, Polizzi A, Spalice A. , et al. The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features. Clin Genet 2015; 87 (05) 401-410
  • 17 Ruggieri M, Praticò AD, Evans DG. Diagnosis, management and new therapeutic options in childhood neurofibromatosis type 2 and related disorders. Semin Pediatr Neurol 2015; 22 (04) 240-258
  • 18 Ruggieri M, Praticò AD, Serra A. , et al. Neurofibromatosi tipo 2 (NF2) e sindromi correlate in età infantile: dalla biologia molecolare alla pratica clinica e nuove terapie con farmaci biologici. Acta Otorhinolaryngol Ital 2016; 36 (05) 345-367
  • 19 Caltabiano R, Magro G, Polizzi A. , et al. A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas. Childs Nerv Syst 2017; 33 (06) 933-940
  • 20 Ruggieri M, Iannetti P, Clementi M. , et al. Neurofibromatosis type 1 and infantile spasms. Childs Nerv Syst 2009; 25 (02) 211-216
  • 21 Ruggieri M. Familial hypomelanosis of ito: implications for genetic counselling. Am J Med Genet 2000; 95 (01) 82-84
  • 22 Ruggieri M, Magro G, Ruggieri M, Polizzi A. Tumors and hypomelanosis of Ito. Arch Pathol Lab Med 2001; 125 (05) 599-601
  • 23 Ruggieri M, Mastrangelo M, Spalice A. , et al. Bilateral (perisylvian and opercular) polymicrogyria and neurofibromatosis type 1. Am J Med Genet 2011; 155 A (03) 582-585
  • 24 Pavone P, Praticò AD, Ruggieri M, Falsaperla R. Hypomelanosis of Ito: a round on the frequency and type of epileptic complications. Neurol Sci 2015; 36 (07) 1173-1180
  • 25 Sukhudyan B, Jaladyan V, Melikyan G, Schlump JU, Boltshauser E, Poretti A. Gómez-López-Hernández syndrome: reappraisal of the diagnostic criteria. Eur J Pediatr 2010; 169 (12) 1523-1528
  • 26 Rush ET, Adam MP, Clark RD. , et al. Four new patients with Gomez-Lopez-Hernandez syndrome and proposed diagnostic criteria. Am J Med Genet A 2013; 161A (02) 320-326
  • 27 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
  • 28 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Rediagnosing one of Smith's patients (John McCann) with “neuromas tumours” (1849). Neurol Sci 2017; 38 (03) 493-499
  • 29 Ruggieri M, Praticò AD, Scuderi A, Sorge G, Polizzi A. The multiple faces of artwork diagnoses. Lancet Neurol 2017; 16 (06) 417-418
  • 30 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Early history of the different forms of neurofibromatosis from ancient Egypt to the British Empire and beyond: first descriptions, medical curiosities, misconceptions, landmarks, and the persons behind the syndromes. Am J Med Genet A 2018; 176 (03) 515-550
  • 31 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
  • 32 Gomez MR. Cerebello-trigeminal-dermal dysplasia. In: Gomez MR. , ed. Neurocutaneous Diseases. A Practical Approach. Stoneham, Butterworths: 1987: 345-348
  • 33 López-Hernández A. Craniosynostosis, ataxia, trigeminal anaesthesia and parietal alopecia with pons-vermis fusion anomaly (atresia of the fourth ventricle). Report of two cases. Neuropediatrics 1982; 13 (02) 99-102
  • 34 Pascual-Castroviejo I. Displasia cerebelotrigeminal. Neurologic infantile, Barcelona (Editorial) Cientifico-medica: In: Pediatric Neurology [Neurología infantil] [In Spanish]. Vol. 1. Barcelona, Editorial Científico-Médico; 1983: 680
  • 35 Kayser B. Ein fall von angeborener trigeminuslähmung und angeborenem totalem tränenmangel. Klin Mel Augenheilkd 1921; 66: 652-654
  • 36 Gross H. Die rhombencephalosynapsis, eine systemisierte Kleinhirnfehlbildung. Arch Psychiatr Zeitsch Neurol 1959; 199: 537-552
  • 37 Pillat A. Wiener ophthalmologische gesellschaft epithelschadigung der hornhaut bei angeborener trigeminushypoplasie. Wien Klin Wochenschr 1949; 61: 605
  • 38 Truwit CL, Barkovich AJ, Shanahan R, Maroldo TV. MR imaging of rhombencephalosynapsis: report of three cases and review of the literature. Am J Neuroradiol 1991; 12 (05) 957-965
  • 39 Pavone P, Incorpora G, Ruggieri M. A complex brain malformation syndrome with rhombencephalosynapsis, preaxial hexadactyly plus facial and skull anomalies. Neuropediatrics 2005; 36 (04) 279-283
  • 40 Tan TY, McGillivray G, Goergen SK, White SM. Prenatal magnetic resonance imaging in Gomez-Lopez-Hernandez syndrome and review of the literature. Am J Med Genet A 2005; 138 (04) 369-373
  • 41 Ruggieri M, Iannetti P, Pavone L. Delineation of a newly recognized neurocutaneous malformation syndrome with “cutis tricolor”. Am J Med Genet A 2003; 120A (01) 110-116
  • 42 Ruggieri M, Iannetti F, Polizzi A. , et al. Cataracts in three children with a newly recognised neurocutaneous malformation phenotype with "cutis tricolor". Br J Ophthalmol 2009; 93: 127-128
  • 43 Ruggieri M, Roggini M, Kennerknecht I, Polizzi A, Distefano A, Pavone V. Spectrum of skeletal abnormalities in a complex malformation syndrome with “cutis tricolor” (Ruggieri-Happle syndrome). Acta Paediatr 2011; 100 (01) 121-127
  • 44 Nicita F, Spalice A, Roggini M. , et al. Complex malformation (Ruggieri-Happle) phenotype with “cutis tricolor” in a 10-year-old girl. Brain Dev 2012; 34 (10) 869-872
  • 45 Ruggieri M, Polizzi A, Schepis C. , et al. Cutis tricolor: a literature review and report of five new cases. Quant Imaging Med Surg 2016; 6 (05) 525-534
  • 46 Lionetti E, Pavone P, Kennerknecht I. , et al. Neurological manifestations in individuals with pure cutaneous or syndromic (Ruggieri-Happle syndrome) phenotypes with “cutis tricolor”: a study of 14 cases. Neuropediatrics 2010; 41 (02) 60-65
  • 47 Papetti L, Tarani L, Nicita F. , et al. Macrocephaly-capillary malformation syndrome: description of a case and review of clinical diagnostic criteria. Brain Dev 2012; 34 (02) 143-147
  • 48 Ruggieri M, Milone P, Pavone P. , et al. Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke-Davidoff-Masson type in two patients. Am J Med Genet A 2012; 158A (11) 2870-2880
  • 49 Ruggieri M, Polizzi A, Strano S. , et al. Mixed vascular nevus syndrome: a report of four new cases and a literature review. Quant Imaging Med Surg 2016; 6 (05) 515-524
  • 50 Barbagallo M, Ruggieri M, Incorpora G. , et al. Infantile spasms in the setting of Sturge-Weber syndrome. Childs Nerv Syst 2009; 25 (01) 111-118
  • 51 Ruggieri M, D'Arrigo G, Abbate M, Distefano A, Upadhyaya M. Multiple coronary artery aneurysms in a child with neurofibromatosis type 1. Eur J Pediatr 2000; 159 (07) 477-480
  • 52 Ruggieri M, Packer RJ. Why do benign astrocytomas become malignant in NF1?. Neurology 2001; 56 (07) 827-829
  • 53 Ruggieri M, Polizzi A. Choroidal abnormalities and mental retardation in neurofibromatosis type 1. Lancet 2001; 357 (9252): 311-312
  • 54 Ruggieri M, Pavone V, Tiné A. , et al. Ossifying fibroma of the skull in a patient with neurofibromatosis type 1. Case report. J Neurosurg 1996; 85 (05) 941-944
  • 55 Praticò AD, Falsaperla R, Ruggieri M, Corsello G, Pavone P. Prognostic challenges of SCN1A genetic mutations: report on two children with mild features. J Pediatr Neurol 2016; 14: 82-88
  • 56 Pavone P, Praticò AD, Gentile G. , et al. A neurocutaneous phenotype with paired hypo- and hyperpigmented macules, microcephaly and stunted growth as prominent features. Eur J Med Genet 2016; 59 (05) 283-289
  • 57 Polizzi A, Pavone P, Parano E, Incorpora G, Ruggieri M. Lack of progression of brain atrophy in Aicardi-Goutières syndrome. Pediatr Neurol 2001; 24 (04) 300-302
  • 58 Ruggieri M, Polizzi A. Segmental neurofibromatosis. J Neurosurg 2000; 93 (03) 530-532
  • 59 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
  • 60 Ruggieri M. Mosaic (segmental) neurofibromatosis type 1 (NF1) and type 2 (NF2): no longer neurofibromatosis type 5 (NF5). Am J Med Genet 2001; 101 (02) 178-180
  • 61 Ruggieri M, Praticò AD. Mosaic neurocutaneous disorders and their causes. Semin Pediatr Neurol 2015; 22 (04) 207-233
  • 62 Gomy I, Heck B, Santos AC. , et al. Two new Brazilian patients with Gómez-López-Hernández syndrome: reviewing the expanded phenotype with molecular insights. Am J Med Genet A 2008; 146A (05) 649-657
  • 63 Schell-Apacik CC, Cohen M, Vojta S. , et al. Gomez-Lopez-Hernandez syndrome (cerebello-trigeminal-dermal dysplasia): description of an additional case and review of the literature. Eur J Pediatr 2008; 167 (01) 123-126
  • 64 de Mattos VF, Graziadio C, Machado Rosa RF. , et al. Gómez-López-Hernández syndrome in a child born to consanguineous parents: new evidence for an autosomal-recessive pattern of inheritance?. Pediatr Neurol 2014; 50 (06) 612-615
  • 65 Ishak GE, Dempsey JC, Shaw DW. , et al. Rhombencephalosynapsis: a hindbrain malformation associated with incomplete separation of midbrain and forebrain, hydrocephalus and a broad spectrum of severity. Brain 2012; 135 (Pt 5): 1370-1386
  • 66 Tully HM, Dempsey JC, Ishak GE. , et al. Beyond Gómez-López-Hernández syndrome: recurring phenotypic themes in rhombencephalosynapsis. Am J Med Genet A 2012; 158A (10) 2393-2406
  • 67 Fernández-Jaén A, Fernández-Mayoralas DM, Calleja-Pérez B, Muñoz-Jareño N, Moreno N. Gomez-Lopez-Hernandez syndrome: two new cases and review of the literature. Pediatr Neurol 2009; 40 (01) 58-62
  • 68 Muñoz R MV, Santos AC, Graziadio C, Pina-Neto JM. Cerebello-trigeminal-dermal dysplasia (Gómez-López-Hernández syndrome): description of three new cases and review. Am J Med Genet 1997; 72 (01) 34-39
  • 69 Bonnet C, Roubertie A, Doummar D, Bahi-Buisson N, Cochen de Cock V, Roze E. Developmental and benign movement disorders in childhood. Mov Disord 2010; 25 (10) 1317-1334
  • 70 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
  • 71 Salpietro V, Polizzi A, Bertè LF. , et al. Idiopathic intracranial hypertension: a unifying neuroendocrine hypothesis through the adrenal-brain axis. Neuroendocrinol Lett 2012; 33 (06) 569-573
  • 72 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
  • 73 Iannetti P, Parisi P, Spalice A, Ruggieri M, Zara F. Addition of verapamil in the treatment of severe myoclonic epilepsy in infancy. Epilepsy Res 2009; 85 (01) 89-95
  • 74 Polizzi A, Finocchiaro M, Parano E, Pavone P, Musumeci S, Polizzi A. Recurrent peripheral neuropathy in a girl with celiac disease. J Neurol Neurosurg Psychiatry 2000; 68 (01) 104-105
  • 75 Ruggieri M, Pavone P, Polizzi A. , et al. Ophthalmological manifestations in segmental neurofibromatosis type 1. Br J Ophthalmol 2004; 88 (11) 1429-1433
  • 76 Ruggieri M, McShane MA. Parental view of epilepsy in Angelman syndrome: a questionnaire study. Arch Dis Child 1998; 79 (05) 423-426
  • 77 Pavone P, Pettoello-Mantovano M, Le Pira A. , et al. Acute disseminated encephalomyelitis: a long-term prospective study and meta-analysis. Neuropediatrics 2010; 41 (06) 246-255
  • 78 Pavone P, Falsaperla R, Ruggieri M. , et al. Clinical course of NMDAr encephalitis and effectiveness of cyclosphosphamide treatment. J Pediatr Neurol 2017; 15: 84-89
  • 79 Pavone P, Spalice A, Polizzi A, Parisi P, Ruggieri M. Ohtahara syndrome with emphasis on recent genetic discovery. Brain Dev 2012; 34 (06) 459-468
  • 80 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
  • 81 Distefano G, Praticò AD. Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy. Ital J Pediatr 2010; 36: 63
  • 82 Ruggieri M, Incorpora G, Polizzi A, Parano E, Spina M, Pavone P. Low prevalence of neurologic and psychiatric manifestations in children with gluten sensitivity. J Pediatr 2008; 152 (02) 244-249
  • 83 Vincent A, Jacobson L, Plested P. , et al. Antibodies affecting ion channel function in acquired neuromyotonia, in seropositive and seronegative myasthenia gravis, and in antibody-mediated arthrogryposis multiplex congenita. Ann N Y Acad Sci 1998; 841 (841) 482-496
  • 84 Pavone P, Praticò AD, Vitaliti G. , et al. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr 2014; 40: 79
  • 85 Spalice A, Ruggieri M, Grosso S. , et al. Dysembryoplastic neuroepithelial tumors: a prospective clinicopathologic and outcome study of 13 children. Pediatr Neurol 2010; 43 (06) 395-402
  • 86 Pavone P, Praticò AD, Rizzo R. , et al. A clinical review on megalencephaly: A large brain as a possible sign of cerebral impairment. Medicine (Baltimore) 2017; 96 (26) e6814
  • 87 Ruggieri M, Polizzi A, Pavone L, Musumeci S. Thalamic syndrome in children with measles infection and selective, reversible thalamic involvement. Pediatrics 1998; 101 (1 Pt 1): 112-119
  • 88 Barkovich AJ. Congenital malformations of the brain and skull. In: Barkovich AJ. , ed. Pediatric Neuroimaging. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2005: 291459
  • 89 Toelle SP, Yalcinkaya C, Kocer N. , et al. Rhombencephalosynapsis: clinical findings and neuroimaging in 9 children. Neuropediatrics 2002; 33 (04) 209-214
  • 90 Purvis DJ, Ramirez A, Roberts N, Harper JI. Gomez-Lopez-Hernandez syndrome: another consideration in focal congenital alopecia. Br J Dermatol 2007; 157 (01) 196-198
  • 91 Tan E, Ng M, Giam YC. Temporal triangular alopecia: report of five cases in Asian children. Pediatr Dermatol 2002; 19 (02) 127-128
  • 92 Chandravanshi SL. Encephalocraniocutaneous lipomatosis: a case report and review of the literature. Indian J Ophthalmol 2014; 62 (05) 622-627