scholarly journals Novel Variant in PLAG1 in a Familial Case with Silver–Russell Syndrome Suspicion

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1461
Author(s):  
Yerai Vado ◽  
Arrate Pereda ◽  
Isabel Llano-Rivas ◽  
Nerea Gorria-Redondo ◽  
Ignacio Díez ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Genetic Disorder ◽  
Panel Study ◽  
Uniparental Disomy ◽  
Postnatal Growth ◽  
Triangular Face ◽  
Chromosome 11P15 ◽  
Postnatal Growth Retardation ◽  
Feeding Difficulties ◽  
Silver Russell Syndrome

Silver–Russell syndrome (SRS) is a rare growth-related genetic disorder that is mainly associated with prenatal and postnatal growth retardation. Molecular causes are not clear in all cases, the most common ones being loss of methylation on chromosome 11p15 (≈50%) and maternal uniparental disomy for chromosome 7 (upd(7)mat) (≈10%). However, pathogenic variants in genes such as CDKN1C, HMGA2, IGF2, or PLAG1 have also been described. Previously, two families and one sporadic case have been reported with PLAG1 alterations. Here, we present a case of a female with clinical suspicion of SRS (i.e., intrauterine and postnatal growth retardation, triangular face, psychomotor delay, speech delay, feeding difficulties). No alterations in methylation or copy number were detected at chromosomes 11p15 and 7 using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The custom panel study by next-generation sequencing (NGS) revealed a frameshift variant in the PLAG1 gene (NM_002655.3:c.551delA; p.(Lys184Serfs *45)). Familial studies confirmed that the variant was inherited from the mother and it was also present in other family members. New evidence of pathogenic alterations in the HMGA2-PLAG1-IGF2 pathway suggest the importance of studying and taking into account these genes as alternative molecular causes of Silver–Russell syndrome.

scholarly journals Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 588
Author(s):  
Pierpaola Tannorella ◽  
Daniele Minervino ◽  
Sara Guzzetti ◽  
Alessandro Vimercati ◽  
Luciano Calzari ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Molecular Mechanisms ◽  
Uniparental Disomy ◽  
Postnatal Growth ◽  
Molecular Diagnostic ◽  
Growth Delay ◽  
Molecular Defect ◽  
Maternal Uniparental Disomy ◽  
Feeding Difficulties ◽  
Silver Russell Syndrome

Silver Russell Syndrome (SRS, MIM #180860) is a rare growth retardation disorder in which clinical diagnosis is based on six features: pre- and postnatal growth failure, relative macrocephaly, prominent forehead, body asymmetry, and feeding difficulties (Netchine–Harbison clinical scoring system (NH-CSS)). The molecular mechanisms consist in (epi)genetic deregulations at multiple loci: the loss of methylation (LOM) at the paternal H19/IGF2:IG-DMR (chr11p15.5) (50%) and the maternal uniparental disomy of chromosome 7 (UPD(7)mat) (10%) are the most frequent causes. Thus far, about 40% of SRS remains undiagnosed, pointing to the need to define the rare mechanisms in such a consistent fraction of unsolved patients. Within a cohort of 176 SRS with an NH-CSS ≥ 3, a molecular diagnosis was disclosed in about 45%. Among the remaining patients, we identified in 3 probands (1.7%) with UPD(20)mat (Mulchandani–Bhoj–Conlin syndrome, OMIM #617352), a molecular mechanism deregulating the GNAS locus and described in 21 cases, characterized by severe feeding difficulties associated with failure to thrive, preterm birth, and intrauterine/postnatal growth retardation. Our patients share prominent forehead, feeding difficulties, postnatal growth delay, and advanced maternal age. Their clinical assessment and molecular diagnostic flowchart contribute to better define the characteristics of this rare imprinting disorder and to rank UPD(20)mat as the fourth most common pathogenic molecular defect causative of SRS.

scholarly journals Silver Russell syndrome in a  preterm girl with 8q12.1 deletion encompassing PLAG1.

2021 ◽  
Author(s):  
José Ramón Fernández-Fructuoso ◽  
Cristina De la Torre-Sandoval ◽  
Madeleine Harbison ◽  
Sandra Chantot-bastaraud ◽  
I. Temple ◽  
...  
Keyword(s):  
Clinical Features ◽  
Growth Retardation ◽  
Intrauterine Growth Retardation ◽  
De Novo ◽  
Postnatal Growth ◽  
Postnatal Growth Retardation ◽  
Feeding Difficulties ◽  
Intrauterine Growth ◽  
Molecular Features ◽  
Silver Russell Syndrome

Silver Russell syndrome (SRS) is a congenital disorder characterised by intrauterine growth retardation (IUGR), feeding difficulties and postnatal growth retardation. In a small number of cases PLAG1 variants have been described (OMIM #618907). PLAG1 haploinsufficiency decreases IGF2 expression and produces a Silver Russell syndrome like phenotype. Here, we describe the phenotype and molecular features of a 26 months girl with clinical features of SRS and a de novo 2.1 Mb deletion encompassing PLAG1 is reported in association with clinical features suggestive of SRS.

scholarly journals Torticollis as the Main Presentation in a Child with Russell-Silver Syndrome: A Case Report

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Mohsen Javadzadeh ◽  
Hedieh Saneifard ◽  
Amir Hossein Hosseini
Keyword(s):  
Genetic Disorder ◽  
Postnatal Growth ◽  
The Body ◽  
Poor Growth ◽  
Triangular Face ◽  
Postnatal Growth Retardation ◽  
Significant Difference ◽  
Males And Females ◽  
Silver Syndrome ◽  
Two Sides

Russell-Silver syndrome is a genetic disorder the inheritance pattern of which is mostly sporadic. Some of the features of the syndrome are present at birth, and others appear in later years. The main clinical features include low birth weight, poor growth postnatally, short height, and discrepancies in size between the two sides of the body Abu-Amera et al. (2008), Binder et al. (2011). There is no statistical significant difference in prevalence between males and females. We report a case of Russell-Silver syndrome with intrauterine and postnatal growth retardation, triangular face, and body asymmetry, in addition to torticollis as a novel manifestation. In neck sonography, we found asymmetry of sternocleidomastoid muscles. In conclusion, we describe torticollis as a presentation of Russell-Silver syndrome.

Genetic Screening for Maternal Uniparental Disomy of Chromosome 7 in Prenatal and Postnatal Growth Retardation of Unknown Cause

PEDIATRICS ◽  
2002 ◽  
Vol 109 (3) ◽  
pp. 441-448 ◽  
Author(s):  
K. Hannula ◽  
M. Lipsanen-Nyman ◽  
P. Kristo ◽  
I. Kaitila ◽  
K. O. J. Simola ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Genetic Screening ◽  
Uniparental Disomy ◽  
Postnatal Growth ◽  
Chromosome 7 ◽  
Postnatal Growth Retardation ◽  
Maternal Uniparental Disomy

Novel missense mutation in the IGF-I receptor L2 domain results in intrauterine and postnatal growth retardation

2012 ◽  
Vol 77 (2) ◽  
pp. 246-254 ◽  
Author(s):  
Yuki Kawashima ◽  
Katsumi Higaki ◽  
Toshiaki Fukushima ◽  
Fumihiko Hakuno ◽  
Jun-ichi Nagaishi ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Growth Retardation ◽  
Postnatal Growth ◽  
Postnatal Growth Retardation ◽  
Igf I

scholarly journals Phenotype of genetically confirmed Silver-Russell syndrome beyond childhood

2020 ◽  
Vol 57 (10) ◽  
pp. 683-691 ◽  
Author(s):  
Oluwakemi Lokulo-Sodipe ◽  
Lisa Ballard ◽  
Jenny Child ◽  
Hazel M Inskip ◽  
Christopher D Byrne ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Uniparental Disomy ◽  
Scoring Systems ◽  
Hormone Treatment ◽  
Diagnostic Features ◽  
Maternal Uniparental Disomy ◽  
Feeding Difficulties ◽  
Adult Growth ◽  
Silver Russell Syndrome

BackgroundSilver-Russell syndrome is an imprinting disorder that restricts growth, resulting in short adult stature that may be ameliorated by treatment. Approximately 50% of patients have loss of methylation of the imprinting control region (H19/IGF2:IG-DMR) on 11p15.5 and 5%–10% have maternal uniparental disomy of chromosome 7. Most published research focuses on the childhood phenotype. Our aim was to describe the phenotypic characteristics of older patients with SRS.MethodsA retrospective cohort of 33 individuals with a confirmed molecular diagnosis of SRS aged 13 years or above were carefully phenotyped.ResultsThe median age of the cohort was 29.6 years; 60.6% had a height SD score (SDS) ≤−2 SDS despite 70% having received growth hormone treatment. Relative macrocephaly, feeding difficulties and a facial appearance typical of children with SRS were no longer discriminatory diagnostic features. In those aged ≥18 years, impaired glucose tolerance in 25%, hypertension in 33% and hypercholesterolaemia in 52% were noted. While 9/33 accessed special education support, university degrees were completed in 40.0% (>21 years). There was no significant correlation between quality of life and height SDS. 9/25 were parents and none of the 17 offsprings had SRS.ConclusionHistorical treatment regimens for SRS were not sufficient for normal adult growth and further research to optimise treatment is justified. Clinical childhood diagnostic scoring systems are not applicable to patients presenting in adulthood and SRS diagnosis requires molecular confirmation. Metabolic ill-health warrants further investigation but SRS is compatible with a normal quality of life including normal fertility in many cases.

PRENATAL AND POSTNATAL DEVELOPMENTAL CONSEQUENCES OF MATERNAL PHENYLKETONURIA

PEDIATRICS ◽  
1966 ◽  
Vol 37 (6) ◽  
pp. 979-986
Author(s):  
Robert O. Fisch ◽  
William A. Walker ◽  
John A. Anderson
Keyword(s):  
Growth Retardation ◽  
Intrauterine Growth Retardation ◽  
Detrimental Effect ◽  
Postnatal Growth ◽  
Maternal Phenylketonuria ◽  
Phenylalanine Level ◽  
Postnatal Growth Retardation ◽  
Intrauterine Growth ◽  
Prenatal Growth ◽  
Abnormal Metabolism

Two children, one homozygous and the other heterozygous for phenylketonuria, born of an untreated phenylketonuric mother were found to exhibit intrauterine growth retardation and persistent postnatal growth retardation. Microcephaly was present in both children at birth. Microcephaly, mental retardation, and growth retardation were present in the heterozygous child at 5 years of age and in the untreated homozygous child at 2 years of age. The possibility that the comparatively high phenylalanine level in the mother's blood and the concomitant abnormal metabolism had a detrimental effect on the child's prenatal growth and predetermined the rate of their postnatal physical as well as mental development, was discussed.

Neonato piccolo, ipotonico, con difficoltà di alimentazione: pensiamo anche alla sindrome di Temple

2021 ◽  
Vol 24 (5) ◽  
pp. 138-140
Author(s):  
Sara Dal Bo ◽  
Claudia Muratori ◽  
Chiara Nardini ◽  
Ilaria Donati ◽  
Anna Maria Magistà ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Uniparental Disomy ◽  
Final Diagnosis ◽  
Early Puberty ◽  
Maternal Uniparental Disomy ◽  
Feeding Difficulties ◽  
Intrauterine Growth ◽  
Imprinting Disorder ◽  
Development Delay ◽  
Temple Syndrome

Temple syndrome is a rare imprinting disorder mainly due to maternal uniparental disomy of the chromosome 14. It represents the main differential diagnosis of Silver-Russell and Prader-Willi syndrome. This syndrome is characterized by growth retardation, hypotonia, difficult feeding, development delay and precocious puberty. The absence of congenital pathognomonic malformations and universally recognized screening methodologies make this pathology be underdiagnosed, so the analysis of 14q32 should be evaluated in all cases of intrauterine growth restriction, hypotonia and neonatal feeding difficulties. It should also be considered in cases of unexplained early puberty associated with poor stature growth. The paper presents the case of a girl with the final diagnosis of Temple syndrome, with an initial picture of intrauterine growth retardation, axial hypotonia and feeding difficulties. The initial diagnostic suspicion was a Silver-Russell syndrome.

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