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Karyotypic analysis from fibroblast cultures obtained from a skin biopsy of the hypopigmented area showing trisomy 2.
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INTRODUCTION: Hypomelanosis of Ito is a rare neurocutaneous disorder, characterized by streaks and swirls of hypopigmentation following the lines of Blaschko that may be associated to systemic abnormalities involving the central nervous system and musculoskeletal system. Despite the preponderance of reported sporadic hypomelanosis of Ito, few repor...
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Context 1
... karyotypic analysis of the peripheral blood cultures of our patient and her father did not reveal any chromosomal anomaly. The karyotypic analysis from fibroblast cultures obtained from a skin biopsy of the hypopigmented area of the father of our patient showed the presence of a trisomy 2 cell line in a 16% mosaic with a normal cell line (karyotype: mos47, XY,+2(15)/46,XY(90); Figure 2). Her parents decided not to authorize the excisional biopsy on their daughter and the fibroblast karyotypic analysis could not be performed. ...
Citations
... [4] Trisomy 2 mosaicism had been previously reported by two authors. [6,7] Differential diagnoses of above condition are as follows: Klippel-Trenaunay syndrome (KTS), CLOVES Syndrome, and PIK3CA-related overgrowth syndrome (PROS). Clinical features of KTS include soft tissue overgrowth, congenital vascular malformation manifesting as port wine stain, varicose veins. ...
Pigmentary mosaicism (PM) is a clinical condition of dyspigmentation with chromosomal abnormality. PM presents with both cutaneous and extracutaneous manifestation.
Hypomelanosis of Ito and linear and whorled nevoid hypermelanosis are syndromic disorders
in which PM is one of the manifestations. We present a case of a 1‑year‑old child with a
unique constellation of symptoms of unilateral syndactyly, hemihypertrophy, and skin
hyperpigmentation. Karyotype from peripheral blood was normal. We found genetic
aberration (mosaic 2q35 deletion) in the present case from fibroblast cultured from the
affected area. This unique constellation of symptoms was previously reported once but genetic
study was not done from the affected tissue. This case highlights the need of considering
fibroblast culture‑based genetic study rather than doing simple karyotype from peripheral
blood. Genetic study also established the molecular basis of symptoms in the above case.
... However, only B20 cases of prenatally detected mosaic trisomy 2 have been reported [37]. Some cases are associated with hypomelanosis of Ito, a neurocutaneous condition involving hypopigmented anomalies that follow the lines of Blaschko [38]. ...
Mosaicism is the presence of two or more genomes in an individual derived from a single zygote. Mosaicism may occur in germ cells (germline mosaicism), potentially causing recurrent aneuploidies in offspring. It may also occur in somatic cells as a postzygotic event. The mosaic events may involve small regions (single nucleotide variants or insertions/deletions) or large chromosomal regions including aneuploidy. Mosaicism may also occur in selected cells across the body or it may be confined to a particular organ or region. Recent next-generation sequencing methods have improved the sensitivity to detect mosaic events, elucidating their roles in a broad range of diseases including aneuploidies, obligate mosaic diseases that are otherwise lethal in the germline, and Mendelian diseases that manifest in a mosaic form.
... The chromosomes involved in pigmentary mosaicism were the following: 2 [22,23] [43,72], and the sex chromosomes [15,16,30,[73][74][75][76][77][78][79][80]. Furthermore, mosaic states with translocations between chromosomes 1, 6, 12, 13, 14 and 21 were found [81][82][83]. ...
Background:
Pigmentary mosaicism is a term that describes varied patterns of pigmentation in the skin caused by genetic heterogeneity of the skin cells. In a substantial number of cases, pigmentary mosaicism is observed alongside extracutaneous abnormalities typically involving the central nervous system and the musculoskeletal system. We have compiled information on previous cases of pigmentary mosaicism aiming to optimize the handling of patients with this condition. Our study is based on a database search in PubMed containing papers written in English, published between January 1985 and April 2017. The search yielded 174 relevant and original articles, detailing a total number of 651 patients.
Results:
Forty-three percent of the patients exhibited hyperpigmentation, 50% exhibited hypopigmentation, and 7% exhibited a combination of hyperpigmentation and hypopigmentation. Fifty-six percent exhibited extracutaneous manifestations. The presence of extracutaneous manifestations in each subgroup varied: 32% in patients with hyperpigmentation, 73% in patients with hypopigmentation, and 83% in patients with combined hyperpigmentation and hypopigmentation. Cytogenetic analyses were performed in 40% of the patients: peripheral blood lymphocytes were analysed in 48%, skin fibroblasts in 5%, and both analyses were performed in 40%. In the remaining 7% the analysed cell type was not specified. Forty-two percent of the tested patients exhibited an abnormal karyotype; 84% of those presented a mosaic state and 16% presented a non-mosaic structural or numerical abnormality. In patients with extracutaneous manifestations, 43% of the cytogenetically tested patients exhibited an abnormal karyotype. In patients without extracutaneous manifestations, 32% of the cytogenetically tested patients exhibited an abnormal karyotype.
Conclusion:
We recommend a uniform parlance when describing the clinical picture of pigmentary mosaicism. Based on the results found in this review, we recommend that patients with pigmentary mosaicism undergo physical examination, highlighting with Wood's light, and karyotyping from peripheral blood lymphocytes and skin fibroblasts. It is important that both patients with and without extracutaneous manifestations are tested cytogenetically, as the frequency of abnormal karyotype in the two groups seems comparable. According to the results only a minor part of patients, especially those without extracutaneous manifestations, are tested today reflecting a need for change in clinical practice.
... However, craniofacial, dental, cardiac, renal, and gonadal abnormalities may also be seen (Table 1). [12][13][14][15][16][17] One of the hallmarks of this disorder is the distinctive pattern of the skin involvement, which is characterized by hypomacular zones with irregular borders, ''V'' or ''S'' shaped striations, swirls, patches, or whorls along the skin cell developmental lines of Blaschko (Fig. 1). These lesions involve mainly the trunk but can occur in the extremities, face, and scalp, usually sparing palms and soles. ...
... Autosomal dominant inheritance has been seen in some cases. 12,15,17 Even though several genetic abnormalities have been reported, the 4 most commons defects are a short arm of X-chromosome (XP11), a short arm of chromosome 12, trisomy of chromosome 18, and triploidy. 17 Failure of X-inactivation may be the cause of sporadic cases. ...
Phakomatoses, also known as neurocutaneous disorders, comprise a vast number of entities that predominantly affect structures originated from the ectoderm such as the central nervous system and the skin, but also the mesoderm, particularly the vascular system. Extensive literature exists about the most common phakomatoses, namely neurofibromatosis, tuberous sclerosis, von Hippel-Lindau and Sturge-Weber syndrome. However, recent developments in the understanding of the molecular underpinnings of less common phakomatoses have sparked interest in these disorders. In this article, we review the clinical features, current pathogenesis, and modern neuroimaging findings of melanophakomatoses, vascular phakomatoses, and other rare neurocutaneous syndromes that may also include tissue overgrowth or neoplastic predisposition.
... Balanced X-autosome translocations, supernumerary X-chromosome ring fragments, ring chromosome 10, and trisomy mosaicism for chromosomes 2,7,9,12,13,14,15,18, and 21 have been documented in up to 50% of HMI cases. [173][174][175][176] Moreover, an association between HI and ring chromosome 20 has been described, 177 as well as between HI and 7.3 Mb de novo duplication of Xp 11.3-p11.4, and random X-inactivation. ...
... Even if blood karyotypes obtained from peripheral lymphocyte cultures were normal in both, a 16% trisomy 2 mosaicism was found in cultured skin fibroblasts derived from a hypopigmented skin area of her father. 173 The recognition of a variety of chromosomal mosaicisms and ring chromosomes was a clue to explain the protean clinical manifestations of this condition and their often asymmetrical expression. The primary question addressed is how such disparate genotypes could produce the common cutaneous phenotype of patchy pigmentation. ...
Hypomelanosis of Ito (HI) is a congenital neurocutaneous syndrome presenting in the first year of life. It was first described by Ito in 1952 as a purely cutaneous disease presenting with skin hypopigmentation. Several extracutaneous manifestations were later described, and it is now known that several organs can be involved (including brain, muscle, bone, heart, eye, kidney, and teeth) and that the prognosis is strictly related to the number of involved organs. The incidence and prevalence of this syndrome have been estimated to range between 1 in 7,540 births and 1 in 82,000; the disorder affects both the sexes, occurs in all races, and is characterized by depigmentation of the skin along the lines of Blaschko on the trunk and extremities in whorled and linear streaks and patterns. The pathogenesis is unknown, but it is likely to be multifactorial. Several models of inheritance have been proposed but not proved; genetic mosaicism is nowadays the most likely explanation for its inheritance. The differential diagnosis comprises other disorders with hypopigmentation following the lines of Blaschko and thus includes the atrophic/hypopigmented (fourth) stage manifestations of incontinentia pigmenti of the Bloch–Sulzberger type, tuberous sclerosis complex, vitiligo, and skin fungal infections. Consensus recommendations for the screening of associated extracutaneous conditions do not exist and management is symptomatic, but a regular evaluation of somatic growth, neurodevelopment, endocrine status, eyes, and teeth should be performed, and the screening of renal function is also advisable. HI still represents a challenging disorder for the child neurologist and a controversial issue in the medical literature. Awareness of this disorder could allow an early diagnosis and appropriate genetic counseling and screening.
... It is thought that HI has phenotypic variability and genetic difference. 8 Various chromosomal alterations like translocation aneuploidy, mosaicism, trisomy and deletion may be seen. Though karyotyping could not be done in our patient, the association of obesity, increased height, gynaecomastia and features of hypogonadism suggest a chromosomal abnormality. ...
Hypomelanosis of Ito is a rare neurocutaneous syndrome. Cutaneous involvement is characterised by streaks and swirls of hypopigmentation arranged in a Blaschkoid pattern. Neural involvement along with other systemic features are seen. We report a case of a 13-year-old boy who presented with the characteristic skin involvement of hypomelanosis of Ito, mental retardation, teeth abnormalities and gynaecomastia along with psoriasis. © BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.
Hypomelanosis of Ito was first described as incontinentia pigmenti achromians in 1952, in a woman with hypopigmented skin lesions following the lines of Blaschko. The sporadic-occurring hypomelanosis of Ito belongs to a group of neurodermatoses with mosaic phenotypes. The disorder has an incidence of 1/3000–10,000 live births with an approximate ratio of 2 females to 1 male. Multiple organ systems may be involved including the brain, musculoskeletal and cardiovascular systems, eyes, kidneys, teeth, and nails. The clinical symptom, diagnosis, and management options are reviewed in this chapter.
Hypomelanosis of Ito (HI) is a rare neuroectodermal disorder first described by Ito in 1952. We report the case of a boy with unusual facial features, cranial asymmetry, right cleft lip and alveolus, and submucous cleft palate who underwent cheiloplasty for right cleft lip and rhinocanthectomy 3 months after birth. At the age of 1 year, cranial deformation and ventriculomegaly of right cerebral hemisphere were diagnosed on head computed tomography. As a result of a detailed examination, he was given a diagnosis of HI because of hypomelanosis of right face, ventriculomegaly of right cerebral hemisphere, right hemihypertrophy, and psychomotor retardation. At the age of 1 year 9 months, palatoplasty and rhinoplasty were performed. Because HI with ventriculomegaly of the cerebral hemisphere and cleft lip and palate is rare, neurological abnormalities such as psychomotor retardation should be evaluated in depth if skin abnormalities such as hypomelanosis appear.
Hypomelanosis of Ito, initially referred to as incontinentia pigmenti achromians, is a rare neurocutaneous disorder. Hypopigmented lesions following the lines of Blaschko are usually the presenting feature. Multiple organ systems can be involved including brain, musculoskeletal, cardiovascular, eyes, kidneys, and teeth. The neurologic complications can include seizures, hemimegalencephaly, developmental delay and abnormalities in tone. Genetic mosaicism is the most likely explanation for its inheritance. It must be distinguished from incontinentia pigmenti because at early stages, skin lesions can appear similar between the two conditions. Consensus recommendations for screening of associated extracutaneous conditions do not exist and management is symptomatic, but regular evaluation of somatic growth, neurodevelopment, endocrine status, eyes, and teeth should occur. Initial screening of renal function has also been recommended. Awareness of this disorder will allow for diagnosis, genetic counseling and appropriate screening.
