Genodermatosis

Genodermatoses alludes to a set of inherited dermatologic disorders. A significant variety of these disorders is unusual and present with oral indications called oral genodermatoses. They typically present with multisystem association prompting an expanded tempo of morbidity and mortality. The oral findings maybe perhaps distinct and may offer the primary clue of underlying genetic disorder. The present article discusses various genodermatomes presenting with oral manifestations and an approach to the diagnosis of these disorders.

, ditandai dengan nodus atau plak subkutan di area kulit yang terbatas/terlokalisasi. Kutis marmorata fisiologis ditandai oleh "patch" eritematosa yang tersusun retikuler dan membentuk gambaran seperti marmer. Lesi kulit ini merupakan respons vaskular tubuh bayi terhadap suhu dingin. Kondisi ini hilang timbul sesuai perubahan suhu lingkungan. Pada makalah ini dilaporkan satu kasus nekrosis lemak subkutan pada BBL disertai dengan kutis marmorata fisiologis. Diagnosis ditegakkan berdasarkan pemeriksaan klinis dan histopatologis. Faktor risiko yang ditemukan berupa riwayat asfiksia saat lahir dan riwayat preeklamsi berat pada ibu selama hamil. Tujuan laporan kasus ini adalah untuk meningkatkan kewaspadaan klinisi terhadap kelainan kulit yang mungkin dijumpai pada bayi baru lahir dan diharapkan dapat meningkatkan kemampuan dalam mendiagnosis dan mengelola kasus nekrosis lemak subkutan. Kata kunci: Subcutaneous fat necrosis of the newborn, nekrosis lemak subkutan, kutismarmorata fisiologis

Abstract: Growth retardation, alopecia, pseudoanodontia, optic atrophy
(GAPO) syndrome is a rare autosomal recessive disorder. The molecular
nature of the disease is not fully understood and is considered to be one of
the ectodermal dysplasia defects. In this report, we describe clinical, histologic,
and ultrastructural features in two siblings born to consanguineous
parents with a brief review of the literature.

Dermatology, being the specialized study of skin
diseases, comprises of an important subdivision of the
practice of medicine not only because of the various
primary diseases affecting the skin, but also because of
the common cutaneous manifestations of deeper
visceral or systemic diseases.Therefore, it is of utmost importance for a dentist to recognize that not only some dermatoses exhibit
concomitant lesions of the oral mucous membranes but
also manifestations of some diseases may be preceded
by oral lesions.

Abstract
Epidermolysis bullosa (EB), a phenotypically heterogeneous group of skin fragility disorders, is characterized by blistering and erosions with considerable morbidity and mortality. Mutations in as many as 18 distinct genes expressed at the cutaneous basement membrane zone have been shown to be associated with the blistering phenotype, attesting to the role of the corresponding proteins in providing stable association of the epidermis to the dermis through adhesion at the dermo-epidermal basement membrane zone. Thus, different forms of EB have been highly instructive in providing information on the physiological functions of these proteins as integral components of the supramolecular adhesion complexes. In addition, precise information of the underlying genes and distinct mutations in families with EB has been helpful in subclassification of the disease with prognostic implications, as well as for prenatal testing and preimplantation genetic diagnosis. Furthermore, knowledge of the types of mutations is prerequisite for application of allele-specific treatment approaches that have been recently developed, including read-through of premature termination codon mutations and chaperone-facilitated intracellular transport of conformationally altered proteins to proper physiologic subcellular location. Collectively, EB serves as a paradigm of heritable skin diseases in which significant progress has been made in identifying the underlying genetic bases and associated aberrant pathways leading from mutations to the phenotype, thus allowing application of precision medicine for this, currently intractable group of diseases.

Keywords
Epidermolysis bullosa; heritable blistering diseases; cutaneous basement membrane zone; type VII collagen

Abstract: Associations of autoimmune diseases
with neurofibromatosis type 1 have been rarely described.
In the present report, we describe two patients
of neurofibromatosis type 1 having an association with
vitiligo in one, and alopecia areata and autoimmune
thyroiditis in another. The associations of neurofibromatosis
type 1 with vitiligo, alopecia areata, and autoimmune
thyroiditis have not been reported earlier.
Whether these associations reflect a causal relationship
with neurofibromatosis type 1 or are coincidental needs
to be settled.

Ectodermal dysplasias (EDs) are a group of genodermatoses characterized by malformations
of tissues derived from the ectoderm, including the skin, its appendages (hair, nails, sweat
glands), teeth, and the breasts. Ectodermal dysplasia syndactyly syndrome (EDSS) is a rare,
newly described type of ED involving syndactyly. We report 2 Yemeni siblings with typical
EDSS manifestations, including bilateral, partial cutaneous syndactyly of the fingers and toes;
sparse, coarse, brittle scalp hair, eyebrows, and eyelashes; and conical, widely spaced teeth with
enamel notches. In addition, the siblings presented with other features hitherto not described for
this syndrome, such as adermatoglyphia, onychogryphosis, hypoplastic widely spaced nipples,
hypoplastic thumbs, and red scalp hair.

Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis caused by a mutation in the NEMO (Nuclear factor kappa β essential modulator) gene on chromosome Xq28 that affects mostly females and is usually lethal in utero for males, and its expression has variety in women. IP is a systemic disease that can cause skin disorders, various defects of the central nervous system, teeth, eyes and skeletal systems. The cutaneous lesions are arranged along the lines of Blaschko and affects the skin in four stages: vesicular, verrucous, hyperpigmented, and atrophic stage.1-6
The definite diagnosis is made by molecular examination, that is mutation in the NEMO gene at Xq28. Clinically, the diagnosis is define by the typical cutaneous lesions that arranged along the lines of Blaschko.4
This case report highlights diagnosis establishment of incontinentia pigmenti for 4 baby ages 2 days, 15 days, 7 months and 15 months. The diagnosed were based on clinical setting, with the typical skin lesions arranged on the lines of Blaschko and two of them were accompanied by the extracutaneous manifestations.

Abstract: Individuals with inherited skin diseases often pose one
of the most difficult diagnostic challenges in dermatology. The
hunt for the underlying molecular pathology may involve
candidate gene screening or linkage analysis, which is usually
determined by the initial history, the physical findings and
laboratory tests. Recent technical advances in DNA sequencing,
however, are shifting the diagnostic paradigm. Notably, nextgeneration
sequencing allows a more comprehensive approach to
diagnosing inherited diseases, with potential savings of both time
and money. In the setting of a paediatric dermatology genetics
clinic in Kuwait, we therefore performed whole-exome sequencing
on seven individuals without a priori detailed knowledge of the
patients’ disorders: from these sequencing data, we diagnosed
X-linked hypohidrotic ectodermal dysplasia (two cases),
acrodermatitis enteropathica, recessive erythropoietic
protoporphyria (two siblings) and localized recessive dystrophic
epidermolysis bullosa (two siblings). All these groups of disorders
are clinically and genetically heterogeneous, but the sequencing
data proved inherently useful in improving patient care and
avoiding unnecessary investigations. Our observations highlight
the value of whole-exome sequencing, in combination with robust
bioinformatics analysis, in determining the precise molecular
pathology and clinical diagnosis in patients with genetic skin
disorders, notably at an early stage in the clinical evaluation of
these often complex disorders and thereby support a new
paradigm for future diagnostics.
Abbreviations: NGSnext, generation sequencing; WGS, whole, genome
sequencing; WES, whole, exome sequencing; PolyPhen-2, polymorphism
phenotyping version-2; SIFT, sorting intolerant from tolerant; HED,
hypohidrotic ectodermal dysplasia; AE, acrodermatitis enteropathica; EPP,
erythropoietic protoporphyria; EB, epidermolysis bullosa; RDEB, recessive
dystrophic epidermolysis bullosa.

Only two homozygous nonsense mutations in the epidermal isoform of the
dystonin gene, DST-e, have been reported previously in autosomal recessive
epidermolysis bullosa simplex (EBS); the affected pedigrees were Kuwaiti and
Iranian. This subtype of EBS is therefore considered to be a rare clinicopathological
entity. In this study, we identified four seemingly unrelated Kuwaiti families
in which a total of seven individuals had predominantly acral trauma-induced
blistering since infancy. All affected individuals were homozygous for the mutation
p.Gln1124* in DST-e, the same mutation that was identified in the originally
reported family from Kuwait. Haplotype analysis in the five pedigrees (including
the previous case) revealed a shared block of ~60 kb of genomic DNA across the
site of the mutation, consistent with a founder effect. Most heterozygotes had no
clinical abnormalities although one subject had mild transient skin fragility during
childhood, an observation noted in the previously reported Iranian pedigree,
suggesting that the condition may also be semidominant in some pedigrees
rather than purely autosomal recessive. Our study reveals propagation of a
mutant ancestral allele in DST-e throughout Kuwait, indicating that this subtype
of EBS may be more common in Kuwait, and perhaps other Middle Eastern
countries, than is currently appreciated.

RESUMEN
La incontinencia pigmenti (síndrome de Bloch-Sulzberger) es una genodermatosis rara causada por una mutación en el gen NEMO localizado en el cromosoma X. Las manifestaciones cutáneas son marcadoras de esta entidad y se dan de forma temprana y cronológica. El compromiso extra cutáneo se da hasta en el 80% de los casos y las alteraciones neurológicas y oftalmológicas son marcadores del  pronóstico porque tienen el potencial de producir secuelas irreversibles. Se presenta el caso de una paciente que desde el primer día de vida inició con lesiones cutáneas que, con la evolución, desarrollaron características clásicas de una incontinencia pigmenti. Se resalta el antecedente familiar asociado, el compromiso neurológico extenso y la importancia de un manejo multidisciplinario.
ABSTRACT
Incontinentia pigmenti (Bloch-Sulzberger Syndrome) is a rare genodermatosis. The disease is X-linked and the most common molecular defect includes mutations in the NEMO gene on chromosome Xq28 in approximately 70% of patients. It is characterized by a multisystem compromise in which the skin manifestations occur in all patients. Also, the dermatological findings occur early and in chronological order. The prevalence of extra skin compromise is approximately 80% of patients. The ophthalmological and neurological manifestations are the major cause of disability in patients and may have a great impact on the quality of life. Some of damages are irreversible. We present the clinical case of a child on her first day of life. It began with skin manifestations typical of incontinentia pigmenti and extensive neurological involvement. In addition, the family history includes a sister with the disease. A multidisciplinary approach is necessary to care for patients and to detect and prevent long-term complications.
RESUMO
A incontinência pigmenti (síndrome de Bloch-Sulzberger) é uma genodermatose rara causada por uma mutação no gene NEMO localizado no cromossoma X. As manifestações cutâneas são marcadoras desta entidade E se dá de forma precoce e cronológica. O compromisso extra cutâneo se dá até em 80% dos casos e as  alterações neurológicas e oftalmológicas são marcadores do prognóstico porque tem o potencial de produzir sequelas irreversíveis. Se apresenta o caso de uma paciente que desde o primeiro dia de vida iniciou com lesões cutâneas que, com a evolução, desenvolveram  características clássicas de uma incontinência pigmenti. Se ressalta o antecedente familiar associado, o compromisso neurológico extenso e a importância de um manejo multidisciplinar.

Nekrosis lemak subkutan pada bayi lelaki baru lahir merupakan panikulitis yang jarang terjadi. Kelainan ini dijumpai pada bayi baru lahir (BBL) cukup bulan atau lebih bulan, ditandai dengan nodus atau plak subkutan di area kulit yang terbatas/terlokalisasi. Kutis marmorata fisiologis ditandai oleh "patch" eritematosa yang tersusun retikuler dan membentuk gambaran seperti marmer. Lesi kulit ini merupakan respons vaskular tubuh bayi terhadap suhu dingin. Kondisi ini hilang timbul sesuai perubahan suhu lingkungan. Pada makalah ini dilaporkan satu kasus nekrosis lemak subkutan pada BBL disertai dengan kutis marmorata fisiologis. Diagnosis ditegakkan berdasarkan pemeriksaan klinis dan histopatologis. Faktor risiko yang ditemukan berupa riwayat asfiksia saat lahir dan riwayat preeklamsi berat pada ibu selama hamil. Tujuan laporan kasus ini adalah untuk meningkatkan kewaspadaan klinisi terhadap kelainan kulit yang mungkin dijumpai pada bayi baru lahir dan diharapkan dapat meningkatkan kemampuan dalam mendiagnosis dan mengelola kasus nekrosis lemak subkutan. Kata kunci: Subcutaneous fat necrosis of the newborn, nekrosis lemak subkutan, kutismarmorata fisiologis SUBCUTANEOUS FAT NECROSIS OF THE NEWBORN ASSOCIATED WITH PHYSIOLOGICAL CUTIS MARMORATA

Olmsted syndrome is a rare disorder characterized by the combination of perioriÞ cial, keratotic plaques and bilateral palmoplantar keratoderma. New associated features are being reported. Olmsted syndrome is particularly rare in a female patient, and we report such a case in a six year-old Indian girl, who presented with keratoderma of her soles since birth and on her palms since the age of two years along with perioral and perinasal hyperkeratosis. She had sparse, light brown, thin hair. Although the psychomotor development of the child was normal until 18 months of age, the keratoderma plaques had restricted the child's mobility after that stage.