New microdeletion and microduplication syndromes: a comprehensive review

Nevado, Julián; Mergener, Rafaella; Palomares‐Bralo, María; Souza, Káren Regina Silva de; Vallespín, Elena; Mena, Rocío; Martínez‐Glez, Víctor; Mori, María Ángeles; Santos, Fernando; García‐Miñaúr, Sixto; García-Santiago, Fé Amalia; Mansilla, Elena; Fernández, Luís; Torres, M. L. de; Riegel, Mariluce; Lapunzina, Pablo

doi:10.1590/s1415-47572014000200007

Cited by 89 publications

(71 citation statements)

References 14 publications

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“…The proband exhibits short stature, microcephaly, developmental delay, moderate intellectual disability, craniofacial dysmorphisms, and hypertelorism, which resembles the phenotype associated with microduplication of 5q35.2q35.3 in the region containing NSD1 in SS (Nevado et al, 2014). Our results also suggest that 12 other genes in the microduplicated 5q35.2q35.3 region could be involved in the pathology of the proband's phenotype.…”

Section: Discussionsupporting

confidence: 59%

A rare case of a boy with de novo microduplication at 5q35.2q35.3 from central Brazil

et al. 2017

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ABSTRACT. Genomic disorders are genetic diseases that are caused by rearrangements of chromosomal material via deletions, duplications, and inversions of unique genomic segments at specific regions. Such rearrangements could result from recurrent non-allelic homologous recombination between low copy repeats. In cases where the breakpoints flank the low copy repeats, deletion of chromosomal segments is often followed by reciprocal duplication. Variations in genomic copy number manifest differently, with duplication and deletions of the same genomic region showing opposite phenotypes. Sotos syndrome is caused by alterations in the dosage of NSD1 on human chromosome 5 by either deletions or mutations, such as microdeletion of 5q35.2q35.3. In general, patients carrying reciprocal microduplication at 5q35.2q35.3 present no clinical phenotype or milder phenotype than do patients with microdeletion at the same locus. We report the first case of 5q35.2q35.3 microduplication encompassing NSD1 in a patient from central Brazil. We identified a genomic imbalance corresponding to a de novo 0.45 Mb microduplication at 5q35.2q35.3 by chromosomal microarray analysis and study of lowcopy repeats. The proband had microduplication in the chromosomal region containing NSD1, which resulted in a Sotos syndrome reversed phenotype, and this duplication was associated with microcephaly, short stature, and developmental delay. Analysis of the genomic structure of the rearranged 5q35.2q35.3 chromosomal region revealed two major low-copy repeat families, which caused the recurrent rearrangements. Chromosomal microarray analysis is a potential tool to identify microrearrangements and guide medical diagnosis, which has to be followed by a non-directive genetic counseling approach to improve the quality of life of the patient.

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Section: Discussionsupporting

confidence: 59%

A rare case of a boy with de novo microduplication at 5q35.2q35.3 from central Brazil

et al. 2017

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“…Physical examination at the age of four years revealed profuse hair on the upper and lower limbs and on the back congenital anomalies (MCA), autistic spectrum disorders (ASD) and other phenotypic fi ndings, associated with intellectual disability (ID). Deletion presents congenital disorders such as diaphragmatic herniae, pulmonary cyst and renal disorders as in our patient (15). Th e diagnosis of CGH should be based on a detailed history, with special attention given to the presence of other anomalies, particularly of the face, teeth, and kidneys (4).…”

Section: Discussionmentioning

confidence: 90%

“…An Irish family with CGHT presented with a coarse face and normal gingivae, AD has also been observed (14), but genetic linkage to 17q24. Apart from diaphragmatic hernia, genital disorders in females and pulmonary cysts, deletion producing MCA also include renal cysts which can cause obstruction/ hydronephrosis (15). Another rare form of CGHT with gingival hyperplasia was previously described showing AR mode of inheritance (11,12,16).…”

Section: Discussionmentioning

confidence: 99%

Congenital Generalized Hypertrichosis Terminalis with Gingival Hyperplasia and a Coarse Face: a Case Report

Kazandjieva

Stefanova

Todorova

et al. 2016

Serbian Journal of Dermatology and Venereology

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Congenital generalized hypertrichosis, in its most common form, is idiopathic. In the absence of underlying endocrine or metabolic disorders, congenital generalized hypertrichosis is rare in humans, affecting as few as one in a billion individuals and may be an isolated condition of the skin, or a component feature of other disorders or syndromes. Congenital generalized hypertrichosis terminalis is an extremely rare condition, a distinct subset of disorders with congenital hypertrichosis, presenting with excessive hair as the primary clinical feature. Congenital generalized hypertrichosis terminalis is characterized by universal excessive growth of pigmented terminal hair and often accompanied with gingival hyperplasia and/or a coarse face. Gingival hyperplasia may be delayed even until puberty. Its pathogenesis may be caused by one of the following mechanisms: conversion of vellus to terminal hairs and/or prolonged anagenetic stage, and/or increase in the number of hair follicles. Since the Middle Ages, less than 60 individuals with congenital hypertrichosis terminalis have been described, and, according to the most recent estimates, less than 40 cases were documented adequately and defi nitively in the literature. Recent articles identifi ed congenital generalized hypertrichosis terminalis as a genomic disorder. This report is a follow up of a six-year-old boy born from the fi rst normal pregnancy of non-consanguineous parents, starting from delivery. Our investigation revealed a history of: excessive hair growth and a coarse face from birth; increased body weight with high blood pressure and gingival hyperplasia at the age of four months. The parents denied any medication or chemical intake during pregnancy, as well as a history of hypertrichosis in their families. The child had a congenital hydronephrosis of the right kidney. Ultrasound and magnetic resonance imaging revealed severe congenital hydronephrosis of the right kidney and suspicion of hypertrophy of the left adrenal gland suggestive of an adenoma. The follow up showed normal values of hormones which excluded adrenal tumor. At the age of 8 months the patient underwent right-sided nephrectomy after several urinary infections. The child was admitted again to our Clinic at the age of four years, with generalized hypertrichosis, gingival hyperplasia and a coarse face without any other pathological signs. He has had a normal intellectual development, but was extremely shy, unconfi dent and dependent on his mother. The relevant laboratory investigations showed normal full blood count, biochemical, hormonal test results and normal function of the single kidney. Molecular chromosome analysis revealed heterozygous deletion on chromosome 17q12 region. Prolonged follow-up with routine checkups every 6-12 months was advised, including regular outpatient appointments particularly with an endocrinologist, because of the risk of diabetes mellitus, and with a nephrologist, for control of renal function. Laser hair removal was suggested and the patient under...

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“…Over the past 3-5 years, high-resolution platforms have identified many small CNVs that underlie ID/DD disorders and therefore may lead to increases in diagnostic yield and the actionable rate for some of these patients. 16 Finally, the comparison with the Riggs criteria is predictive in nature and not a reflection of actual practice. Future studies should be prospective and follow patients for actual clinical management changes.…”

Section: Discussionmentioning

confidence: 99%

Clinical performance of the CytoScan Dx Assay in diagnosing developmental delay/intellectual disability

Pfundt

Kwiatkowski²,

Roter³

et al. 2016

Genetics in Medicine

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New microdeletion and microduplication syndromes: a comprehensive review

Cited by 89 publications

References 14 publications

A rare case of a boy with de novo microduplication at 5q35.2q35.3 from central Brazil

A rare case of a boy with de novo microduplication at 5q35.2q35.3 from central Brazil

Congenital Generalized Hypertrichosis Terminalis with Gingival Hyperplasia and a Coarse Face: a Case Report

Clinical performance of the CytoScan Dx Assay in diagnosing developmental delay/intellectual disability

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