scholarly journals Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Shan Li ◽  
Ke-wang Xi ◽  
Ting Liu ◽  
Ying Zhang ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Clinical Features ◽  
De Novo ◽  
Genetic Disorder ◽  
Deletion Syndrome ◽  
Facial Dysmorphism ◽  
Germline Mosaicism ◽  
Third Generation Sequencing ◽  
Neurological Features ◽  
Hands And Feet ◽  
Abnormal Behaviors

Abstract Background Phelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. The SHANK3 gene is understood to be the critical gene for the neurological features of this syndrome. Case presentation We describe one pair of boy-girl twins with a 22q13 deletion not involving the SHANK3 gene. Interestingly, the clinical and molecular findings of the two patients were identical, likely resulting from germline mosaicism in a parent. The boy-girl twins showed intellectual disability, speech absence, facial dysmorphism, cyanosis, large fleshy hands and feet, dysplastic fingernails and abnormal behaviors, and third-generation sequencing showed an identical de novo interstitial deletion of 6.0 Mb in the 22q13.31-q13.33 region. Conclusions Our case suggests that prenatal diagnosis is essential for normal parents with affected children due to the theoretical possibility of parental germline mosaicism. Our results also indicated that other genes located in the 22q13 region may have a role in explaining symptoms in individuals with PMS. In particular, we propose that four candidate genes, CELSR1, ATXN10, FBLN1 and WNT7B, may also be involved in the etiology of the clinical features of PMS. However, more studies of smaller interstitial deletions with 22q13 are needed to corroborate our hypothesis and better define the genotype-phenotype correlation. Our findings contribute to a more comprehensive understanding of PMS.

Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations

2016 ◽  
Vol 32 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Jung Min Ko ◽  
Jae So Cho ◽  
Yongjin Yoo ◽  
Jieun Seo ◽  
Murim Choi ◽  
...  
Keyword(s):  
De Novo ◽  
Genetic Disorder ◽  
Ductus Arteriosus ◽  
Developmental Dysplasia ◽  
Facial Dysmorphism ◽  
Sequencing Analysis ◽  
Self Mutilation ◽  
Small Hands ◽  
Hands And Feet ◽  
Dysplasia Of The Hip

Wiedemann-Steiner syndrome is a rare genetic disorder characterized by short stature, hairy elbows, facial dysmorphism, and developmental delay. It can also be accompanied by musculoskeletal anomalies such as muscular hypotonia and small hands and feet. Mutations in the KMT2A gene have only recently been identified as the cause of Wiedemann-Steiner syndrome; therefore, only 16 patients from 15 families have been described, and new phenotypic features continue to be added. In this report, we describe 2 newly identified patients with Wiedemann-Steiner syndrome who presented with variable severity. One girl exhibited developmental dysplasia of the hip and fibromatosis colli accompanied by other clinical features, including facial dysmorphism, hypertrichosis, patent ductus arteriosus, growth retardation, and borderline intellectual disability. The other patient, a boy, showed severe developmental retardation with automatic self-mutilation, facial dysmorphism, and hypertrichosis at a later age. Exome sequencing analysis of these patients and their parents revealed a de novo nonsense mutation, p.Gln1978*, of KMT2A in the former, and a missense mutation, p.Gly1168Asp, in the latter, which molecularly confirmed the diagnosis of Wiedemann-Steiner syndrome.

scholarly journals A New Case of 13q12.2q13.1 Microdeletion Syndrome Contributes to Phenotype Delineation

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Giorgia Mandrile ◽  
Eleonora Di Gregorio ◽  
Alessandro Calcia ◽  
Alessandro Brussino ◽  
Enrico Grosso ◽  
...  
Keyword(s):  
Clinical Features ◽  
Critical Region ◽  
Array Cgh ◽  
De Novo ◽  
Genetic Disorder ◽  
Phenotypic Expression ◽  
Microdeletion Syndrome ◽  
Complex Rearrangement

A recently described genetic disorder has been associated with 13q12.3 microdeletion spanning three genes, namely,KATNAL1, LINC00426, andHMGB1. Here, we report a new case with similar clinical features that we have followed from birth to 5 years old. The child carried a complex rearrangement with a double translocation: 46,XX,t(7;13)(p15;q14),t(11;15)(q23;q22). Array-CGH identified ade novomicrodeletion at 13q12.2q13.1 spanning 3–3.4 Mb and overlapping 13q12.3 critical region. Clinical features resembling those reported in the literature confirm the existence of a distinct 13q12.3 microdeletion syndrome and provide further evidence that is useful to characterize its phenotypic expression during the 5 years of development.

Cleft Lip Palate in a Patient with 5q14.3 Deletion Syndrome: A Possible Unreported Feature?

2022 ◽  
pp. 1-8
Author(s):  
Liliana Fernández Hernández ◽  
Miguel A. Alcántara Ortigoza ◽  
Sandra E. Ramos Angeles ◽  
Ariadna González-del Angel
Keyword(s):  
Intellectual Disability ◽  
Sanger Sequencing ◽  
Cleft Lip ◽  
De Novo ◽  
Deletion Syndrome ◽  
Facial Dysmorphism ◽  
Brain Malformations ◽  
Bilateral Cleft Lip ◽  
Cleft Lip Palate ◽  
Distinctive Phenotype

5q14.3 deletion syndrome (MIM#613443) is an uncommon but well-known syndrome characterized by intellectual disability, epilepsy, hypotonia, brain malformations, and facial dysmorphism. Most patients with this syndrome have lost one copy of the <i>MEF2C</i> gene (MIM*600662), whose haploinsufficiency is considered to be responsible for the distinctive phenotype. To date, nearly 40 cases have been reported; the deletion size and clinical spectrum are variable, and at least 6 cases without <i>MEF2C</i> involvement have been documented. We herein report the clinical and cytogenomic findings of an 11-year-old girl who has a 5q14.3q21.1 de novo deletion that does not involve <i>MEF2C</i> but shares the clinical features described in other reported patients. Moreover, she additionally presents with bilateral cleft-lip palate (CLP), which has not been previously reported as a feature of the syndrome. The most frequent syndromic forms of CLP were ruled out in our patient mainly by clinical examination, and Sanger sequencing was performed to discard the presence of a <i>TBX22</i> gene (MIM*300307) defect. Our report suggests CLP as a possible unreported feature and redefines the critical phenotypic regions of 5q14.3 deletion syndrome.

scholarly journals Cerebral White Matter Lesions and Dysmorphisms: Signs Suggestive of 6p25 Deletion Syndrome—Literature Review

2019 ◽  
Vol 08 (04) ◽  
pp. 205-211
Author(s):  
Piero Pavone ◽  
Simona Domenica Marino ◽  
Giovanni Corsello ◽  
Martino Ruggieri ◽  
Danilo Castellano Chiodo ◽  
...  
Keyword(s):  
White Matter ◽  
Developmental Delay ◽  
De Novo ◽  
Clinical Manifestations ◽  
Deletion Syndrome ◽  
Cerebral White Matter ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Perivascular Spaces ◽  
Renal Malformations

AbstractDeletion of the region including chromosome 6p25 has been defined as a syndrome, with more than 68 reported cases. Individuals affected by the syndrome exhibit variable findings, including developmental delay and intellectual disability, cardiac anomalies, dysmorphic features, and—less commonly—skeletal and renal malformations. Ocular and hearing abnormalities are the most notable presenting features. The region encompasses more than 15 genes, of which the FOX group is the most likely causal factor of the clinical manifestations. We report the case of a 2-year-old child with developmental delay, generalized hypotonia, facial dysmorphism, and anomalies involving malformations of the eyes, heart, teeth, and skeleton. The magnetic resonance imaging (MRI) of the child's brain displayed cerebral anomalies involving the white matter, perivascular spaces, and corpus callosum. Array-CGH (comparative genomic hybridization) analysis displayed a de novo partial deletion of the short arm of chromosome 6, extending 5.13 Mb from nt 407.231 to nt 5.541.179. In infancy, neuroradiologic findings of abnormalities in the cerebral white matter and other neurologic anomalies elsewhere in the brain, in association with dysmorphisms and malformations, are highly suggestive of the diagnosis of 6p25 deletion syndrome. When these anomalies are found, the syndrome must be included in the differential diagnosis of disorders affecting the cerebral white matter.

scholarly journals Rubinstein-Taybi syndrome

2004 ◽  
Vol 132 (suppl. 1) ◽  
pp. 109-110
Author(s):  
Slobodanka Grkovic ◽  
Milos Jesic ◽  
Maja Jesic ◽  
Svjetlana Maglajlic
Keyword(s):  
Clinical Features ◽  
Neonatal Period ◽  
Male Child ◽  
Psychomotor Development ◽  
Facial Dysmorphism ◽  
Corrective Surgery ◽  
Hands And Feet ◽  
And Control

Rubinstein-Taybi syndrome is a malformation occurring with approximate incidence of 1 per 10.000 live-born children. The diagnosis is usually based on specific facial dysmorphism in neonatal period, as well as on characteristic deformities of the hands and feet. Our study presents a male child who was diagnosed to have Rubinstein-Taybi syndrome when he was one month old. The child had all characteristic clinical features. In further follow-up period, corrective surgery and control of his psychomotor development are being planned.

scholarly journals Prader-Willi Syndrome due to an Unbalanced de novo Translocation t(15;19)(q12;p13.3)

2016 ◽  
Vol 150 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Vy Dang ◽  
Abhilasha Surampalli ◽  
Ann M. Manzardo ◽  
Stephanie Youn ◽  
Merlin G. Butler ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosome Region ◽  
Genetic Disorder ◽  
Type I ◽  
Prader Willi Syndrome ◽  
Stk11 Gene ◽  
Feeding Difficulties ◽  
First Case ◽  
Increased Risk ◽  
Hands And Feet

Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by endocrine, neurologic, and behavioral abnormalities. We report the first case of an unbalanced de novo reciprocal translocation of chromosomes 15 and 19, 45,XY,-15,der(19)t(15;19)(q12;p13.3), resulting in monosomy for the PWS critical chromosome region. Our patient had several typical features of PWS including infantile hypotonia, a poor suck and feeding difficulties, tantrums, skin picking, compulsions, small hands and feet, and food seeking, but not hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen in PWS at the time of examination at 6 years of age. He had seizures noted from 1 to 3 years of age and marked cognitive delay. High-resolution SNP microarray analysis identified an atypical PWS type I deletion in chromosome 15 involving the proximal breakpoint BP1. The deletion extended beyond the GABRB3 gene but was proximal to the usual distal breakpoint (BP3) within the 15q11q13 region, and GABRA5, GABRG3, and OCA2 genes were intact. No deletion of band 19p13.3 was detected; therefore, the patient was not at an increased risk of tumors from the Peutz-Jeghers syndrome associated with a deletion of the STK11 gene.

scholarly journals Non-classical 1p36 deletion in a patient with Duane retraction syndrome: case report and literature review

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Emiy Yokoyama ◽  
Camilo E. Villarroel ◽  
Sinhué Diaz ◽  
Victoria Del Castillo ◽  
Patricia Pérez-Vera ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Deletion Syndrome ◽  
Clinical Feature ◽  
Facial Dysmorphism ◽  
Case Presentation ◽  
Ocular Manifestations ◽  
Retraction Syndrome ◽  
Duane Retraction Syndrome

Abstract Background Monosomy of 1p36 is considered the most common terminal microdeletion syndrome. It is characterized by intellectual disability, growth retardation, seizures, congenital anomalies, and distinctive facial features that are absent when the deletion is proximal, beyond the 1p36.32 region. In patients with proximal deletions, little is known about the associated phenotype, since only a few cases have been reported in the literature. Ocular manifestations in patients with classical 1p36 monosomy are frequent and include strabismus, myopia, hypermetropia, and nystagmus. However, as of today only one patient with 1p36 deletion and Duane retraction syndrome (DRS) has been reported. Case presentation We describe a patient with intellectual disability, facial dysmorphism, and bilateral Duane retraction syndrome (DRS) type 1. Array CGH showed a 7.2 Mb de novo deletion from 1p36.31 to 1p36.21. Discussion Our patient displayed DRS, which is not part of the classical phenotype and is not a common clinical feature in 1p36 deletion syndrome; we hypothesized that this could be associated with the overlapping deletion between the distal and proximal 1p36 regions. DRS is one of the Congenital Cranial Dysinnervation Disorders, and a genetic basis for the syndrome has been extensively reported. The HES3 gene is located at 1p36.31 and could be associated with oculomotor alterations, including DRS, since this gene is involved in the development of the 3rd cranial nerve and the 6th cranial nerve’s nucleus. We propose that oculomotor anomalies, including DRS, could be related to proximal 1p36 deletion, warranting a detailed ophthalmologic evaluation of these patients.

A Novel 23.1 Mb Interstitial Deletion Involving 7q22.3q32.1 in a Girl with Short Stature, Motor Delay, and Craniofacial Dysmorphism

2015 ◽  
Vol 145 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Maria del Refugio Rivera-Vega ◽  
Luis A. Gómez-del Angel ◽  
Juan M. Valdes-Miranda ◽  
Adrián Pérez-Cabrera ◽  
Luz M. Gonzalez-Huerta ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Short Stature ◽  
De Novo ◽  
Deletion Syndrome ◽  
Congenital Defects ◽  
Facial Dysmorphism ◽  
Motor Delay ◽  
Craniofacial Dysmorphism ◽  
7Q Deletion ◽  
Omim Database

Interstitial deletions of 7q show a wide phenotypic spectrum that varies with respect to the location and size of the deleted region. They lead to craniofacial dysmorphism with intellectual disability, growth retardation, and various congenital defects. Here, a Mexican girl with microcephaly, facial dysmorphism, short stature, hand anomalies, and intellectual disability was analyzed by CytoScan HD array. Her phenotype was associated with a de novo 7q22.3q32.1 deletion involving 109 loci, 57 of them listed in the OMIM database. This novel deletion increases the knowledge of the variability in the rupture sites of the region and expands the spectrum of molecular and clinical defects of the 7q deletion syndrome.

scholarly journals Ring Chromosome 4 in a Child with Multiple Congenital Abnormalities: A Case Report and Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
C. S. Paththinige ◽  
N. D. Sirisena ◽  
U. G. I. U. Kariyawasam ◽  
L. P. C. Saman Kumara ◽  
V. H. W. Dissanayake
Keyword(s):  
Clinical Features ◽  
Congenital Abnormalities ◽  
De Novo ◽  
Ductus Arteriosus ◽  
Ring Chromosome ◽  
Female Child ◽  
Facial Dysmorphism ◽  
Chromosome 4 ◽  
Talipes Equinovarus ◽  
Limb Deformities

A female child born preterm with intrauterine growth retardation and presenting with facial dysmorphism with clefts, microcephaly, limb deformities, and congenital abnormalities involving cardiovascular and urinary systems is described. Chromosomal analysis showed ade novo46,XX,r(4)(p15.3q35) karyotype. The clinical features of the patient were compared with the phenotypic characteristics of 17 previously reported cases with ring chromosome 4 and those with Wolf-Hirschhorn syndrome (4p-). Clinical features observed in this case are consistent with the consensus phenotype in ring chromosome 4. Patent ductus arteriosus and bilateral talipes equinovarus observed in this baby widen the phenotypic spectrum associated with ring chromosome 4.

scholarly journals Expanding the Clinical Spectrum of Sotos Syndrome in a Patient with the New “c.[5867T>A]+[=]”; “p.[Leu1956Gln]+[=]” NSD1 Missense Mutation and Complex Skin Hamartoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3189
Author(s):  
Annalisa Mencarelli ◽  
Paolo Prontera ◽  
Amedea Mencarelli ◽  
Daniela Rogaia ◽  
Gabriela Stangoni ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Clinical Features ◽  
De Novo ◽  
Genetic Disorder ◽  
Control Cell ◽  
Functional Domain ◽  
Sotos Syndrome ◽  
Organ Systems ◽  
Increased Risk ◽  
The Right

Sotos syndrome is one of the most common overgrowth diseases and it predisposes patients to cancer, generally in childhood. The prevalence of this genetic disorder is 1:10,000–1:50,000, and it is characterized by wide allelic heterogeneity, with more than 100 different known mutations in the nuclear receptor-binding SET domain containing protein 1 (NSD1) gene. Most of these alterations are deletions and common micro-deletions with haploinsufficiency. Singular variants are missense mutations. The present study reports a case of a 4-year-old boy with specific clinical features of Sotos syndrome and a particular complex skin hamartoma on the right femoral side, in addition to other minor findings, such as a “café-au-lait” spot on the right hemithorax and syndactyly of the second and third right toes. NSD1 gene analysis identified a de novo missense mutation, “c.[5867T>A]+[=]”; “p.[Leu1956Gln]+[=]”, that was not previously described in the literature. This mutation was localized to the functional domain of the gene and was likely the cause of Sotos syndrome in our patient. We also compared aspects of our patient’s condition with the clinical features of tuberous sclerosis (TSC), which is an autosomal neurocutaneous syndrome caused by mutations in the TSC1/TSC2 genes. These genes control cell growth and cell survival. This disorder is characterized by hamartomas in multiple organ systems, several coetaneous abnormalities, epilepsy, and increased risk of several types of tumors.

Sign in / Sign up

Export Citation Format

Share Document