Michele Callea

Oral rehabilitation of children with ectodermal dysplasia

The aim of this study was to describe the clinical treatment of young patients, affected by ectodermal dysplasia (ED), and to possibly establish clinical guidelines. The study design was case series. ED syndromes (EDs) are a heterogeneous group of inherited diseases characterised by abnormal development of tissues of ectodermal origin. The most common form of EDs is X linked hypohidrotic ED (HED). Characteristic triad of HED is oligo-anodontia, hypotricosis, hypo-anhydrosis. Oligo-anodontia is one of the most severe impairment, since it affects chewing, swallowing, speech, esthetics and social relation. Early prosthetic rehabilitation (at 2–3 years of age), with partial or complete dentures, is essential to improve oral function and reduce the social impairment.

Ear nose throat manifestations in hypoidrotic ectodermal dysplasia

The ectodermal dysplasias (EDs) are a large and complex group of inherited disorders. In various combinations, they all share anomalies in ectodermal derived structures: hair, teeth, nails and sweat gland function. Clinical overlap is present among EDs. Few causative genes have been identified, to date. Altered gene expression is not limited to the ectoderm but a concomitant effect on developing mesenchymal structures, with modification of ectodermal-mesenchymal signaling, takes place. The two major categories of ED include the hidrotic and hypohidrotic form, the latter more frequent; they differentiate each other for the presence or absence of sweat glands. We report Ear Nose Throat manifestations of ED, linked to the reduction of mucous glands in the nasal fossae with reduced ciliar function, and decrease salivary glands function. Often patients report an increased rate of infections of the upper respiratory tract and of the ear. Nasal obstruction due to the presence of nasal crusting, hearing loss and throat hoarseness are the most represented symptoms. Environmental measures, including a correct air temperature and humidification, is mandatory above all in subjects affected by hypohidrotic form.

Infantile bilateral glaucoma in a child with ectodermal dysplasia

Ectodermal dysplasia is a rare disease which affects at least two ectodermal-derived structures such as hair, nails, skin, sweat glands and teeth. Approximately 200 different conditions have been classified as an ectodermal dysplasia and X-linked hypohidrotic ectodermal dysplasia (XHED) represents the commonest form. Clinically, XHED is characterized by hypotrichosis, hypohidrosis and hypodontia. A variety of ocular manifestations have been reported in XHED, the most common being dryness of eyes due to tear deficiency and instability of the film secondary to the absence of meibomian gland function. Here we report a child with the distinctive clinical features of XHED confirmed with molecular diagnosis who presented with infantile bilateral glaucoma, in addition to the classical ocular involvement in XHED.

A new biological approach to guided bone and tissue regeneration.

The purpose of this study was to determine the potential of platelet-rich fibrin (PRF) membranes used for guided bone and tissue regeneration. A patient with insufficient alveolar ridge width in aesthetic zone was enrolled. The patients blood was centrifuged to obtain PRF membranes. Autogenous bone graft was mixed with bovine hydroxyapatite, PRF particles and applied to fill the defect. Five PRF membranes were placed over the bone mix. After 4 months a cone-beam CT was performed to evaluate bone regeneration. The use of PRF as cover membrane permitted a rapid epithelisation and represented an effective barrier versus epithelial cell penetration. After 4 months the site appeared precociously healed and the bone volume increased. This new approach represents a predictable method of augmenting deficient alveolar ridges. Guided bone regeneration with PRF showed limitation compared with guided bone regeneration using collagen membrane in terms of bone gain. The association of collagen membrane and PRF could be a good association.

X‐linked reticulate pigmentary disorder with systemic manifestations: A new family and review of the literature

X‐linked reticulate pigmentation disorder with systemic manifestations (XLPDR) is an extremely rare genodermatosis with recessive X‐linked inheritance but unknown molecular basis. In males, cutaneous involvement is characterized by reticulate hyperpigmentation of the skin that is associated with a typical facies and severe systemic involvement. In the carrier females, manifestations are apparently limited to the skin with patchy linear hyperpigmentation following the lines of Blaschko that are similar to stage III incontinentia pigmenti. Thus far, only five families affected by this disorder have been described. We report on a new family with clinical features of XLPDR and compare it with those reported in the literature.

A new phenotypic variant in cleidocranial dysplasia (CCD) associated with mutation c.391C>T of the RUNX2 gene

The RUNX2 gene is a physiological regulatory gene implicated in the development of cleidocranial dysplasia (CCD). A 13-month-old child presented with clinical features of CCD. At the age of 3 years the diagnosis was corroborated by clinical genetic assessment and DNA analysis, revealing a missense mutation p.R131C (c.391C>T) in RUNX2. At the age of 8 years the child was found to have a unique dental phenotype, represented by lack of supernumerary teeth and congenital absence of one tooth. A simple therapeutic approach was adopted, consisting of interceptive orthodontic treatment. The presence of this specific missense mutation in RUNX2, associated with the lack of typical supernumerary teeth may suggest a phenotype–genotype association.

Identification of a novel frameshift mutation in the EDAR gene causing autosomal dominant hypohidrotic ectodermal dysplasia

References 1 Rongioletti F, Rebora A. Cutaneous reactive angiomatoses. Patterns and classification of reactive vascular proliferation. J Am Acad Dermatol 2003; 49: 887–896. 2 Watanabe T, Yamada N, Yoshida Y, Yamamoto O. Intralymphatic histiocytosis with granuloma formation associated with orthopaedic metal implants. Br J Dermatol 2008; 158: 402–404. 3 Requena L, El-Shabrawi-Caelen L, Walsh SN et al. Intralymphatic histiocytosis: a clinicopathologic study of 16 cases. Am J Dermatopathol 2009; 31: 140–151. 4 Chiu YE, Maloney JE, Bengana C. Erythematous patch overlying a swollen knee–quiz case. Intralymphatic histiocytosis. Arch Dermatol 2010; 146: 1037–1042. 5 Grekin S, Mesfin M, Kang S, Douglas RF. Intralymphatic histiocytosis following placement of a metal implant. J Cutan Pathol 2011; 38: 351–353. 6 Rossari S, Scatena C, Gori A et al. Intralymphatic histiocytosis: cutaneous nodules and metal implants. J Cutan Pathol 2011; 38: 534–535. 7 Saggar S, Lee B, Krivo J, Jacobson M, Krishnamurthy K. Intralymphatic histiocytosis associated with orthopaedic implants. J Drugs Dermatol 2011; 10: 1208–1209. 8 de Unamuno Bustos B, Rabasco AG, Sanchez RB, Aparicio AM, de Miquel VA. Erythematous indurated plaque on the right upper limb. Int J Dermatol 2013; 52: 547–549.

A novel INDEL mutation in the EDA gene resulting in a distinct X- linked hypohidrotic ectodermal dysplasia phenotype in an Italian family.

References 1 Lauria G, Hsieh ST, Johansson O et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol 2010; 17: e44–e49. 2 Backonja MM, Attal N, Baron R et al. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain 2013; 154: 1807–1819. 3 Rolke R, Baron R, Maier C et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006; 123: 231–243. 4 Schneider JC, Harris NL, El Shami A et al. A descriptive review of neuropathic-like pain after burn injury. J Burn Care Res 2006; 27: 524–528. 5 Altun V, Hakvoort TE, van Zuijlen PP, van der Kwast TH, Prens EP. Nerve outgrowth and neuropeptide expression during the remodeling of human burn wound scars. A 7-month follow-up study of 22 patients. Burns 2001; 27: 717–722. 6 Isoardo G, Stella M, Cocito D et al. Neuropathic pain in post-burn hypertrophic scars: a psychophysical and neurophysiological study. Muscle Nerve 2012; 45: 883–890. 7 Schuhknecht B, Marziniak M, Wissel A et al. Reduced intraepidermal nerve fibre density in lesional and nonlesional prurigo nodularis skin as a potential sign of subclinical cutaneous neuropathy. Br J Dermatol 2011; 165: 85–91. 8 Maddison B, Parsons A, Sangueza O, Sheehan DJ, Yosipovitch G. Retrospective study of intraepidermal nerve fiber distribution in biopsies of patients with nummular eczema. Am J Dermatopathol 2011; 33: 621– 623. 9 Berardesca E, Farage M, Maibach H. Sensitive skin: an overview. Int J Cosmet Sci 2013; 35: 2–8. 10 St€ander S, Schneider SW, Weishaupt C, Luger TA, Misery L. Putative neuronal mechanisms of sensitive skin. Exp Dermatol 2009; 18: 417–423. 11 Misery L, Bodere C, Genestet S, Zagnoli F, Marcorelles P. Small-fibre neuropathies and skin: news and perspectives for dermatologists. Eur J Dermatol 2014; 24: 147–153. 12 Benecke H, Lotts T, St€ander S. Investigational drugs for pruritus. Expert Opin Investig Drugs 2013; 22: 1167–1179. 13 Dhaka A, Viswanath V, Patapoutian A. Trp ion channels and temperature sensation. Annu Rev Neurosci 2006; 29: 135–161. 14 Denda M, Tsutsumi M, Denda S. Topical application of TRPM8 agonists accelerates skin permeability barrier recovery and reduces epidermal proliferation induced by barrier insult: role of cold-sensitive TRP receptors in epidermal permeability barrier homoeostasis. Exp Dermatol 2010; 19: 791–795. 15 Peier AM, Reeve AJ, Andersson DA et al. A heat-sensitive TRP channel expressed in keratinocytes. Science 2002; 296: 2046–2049. 16 St€ander S, Zeidler C, Lotts T, R€ ulander F, Dangelmaier J, Luger TA. Update on the antipruritic effect of aprepitant. Actadermato-Venerologica 2013; 5: 610–611. 17 Almeida TA, Rojo J, Nieto PM et al. Tachykinins and tachykinin receptors: structure and activity relationships. Curr Med Chem 2004; 11: 2045–2081. 18 St€ander S, Siepmann D, Herrgott I, Sunderk€ otter C, Luger TA. Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS ONE 2010; 5: e10968.

Phenotypic heterogeneity and mutational spectrum in a cohort of 45 Italian males subjects with X-linked ectodermal dysplasia

Ectodermal dysplasias (EDs) are a group of genetic disorders characterized by the abnormal development of the ectodermal‐derived structures. X‐linked hypohidrotic ectodermal dysplasia, resulting from mutations in ED1 gene, is the most common form. The main purpose of this study was to characterize the phenotype spectrum in 45 males harboring ED1 mutations. The study showed that in addition to the involvement of the major ectodermal tissues, the majority of patients also have alterations of several minor ectodermal‐derived structures. Characterizing the clinical spectrum resulting from ED1 gene mutations improves diagnosis and can direct clinical care.

Acute myeloid leukemia in a 3 years old child with cleidocranial dysplasia

Michele Callea, Emanuele Bellacchio*, Fabiana Fattori*, Enrico Bertini, Francesco Callea and Francisco Cammarata-Scalisi Institute for Maternal and Child Health IRCCS ‘‘Burlo Garofolo’’, Trieste, Italy; Research Laboratories, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; Unit for Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children Hospital, Rome, Italy; Department of Pathology, Bambino Gesù Children Hospital, IRCCS, Rome, Italy; Unit of Medical Genetics, Department of Pediatrics, Faculty of Medicine, University of The Andes, Mérida, Venezuela