Hypopigmented patches in Roberts/SC phocomelia syndrome occur via aneuploidy susceptibility

Sezer, Abdullah; Kayhan, Gülsüm; Zenker, Martin; Perçin, Ferda

doi:10.1016/j.ejmg.2018.12.013

Cited by 8 publications

(8 citation statements)

References 22 publications

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“…Clinical diagnosis of RBS is particularly challenging in individuals with a mild presentation, especially when associated with rare malformations. Karyotyping can help in establishing the diagnosis of RBS as premature centrosome separation and separation of the heterochromatic regions are observed as characteristic chromosomal abnormalities in lymphocytes of individuals with biallelic ESCO2 mutations (Goh et al, 2010; Gordillo et al, 1993; Sezer, Kayhan, Zenker, & Percin, 2019). Here we describe a 3‐year‐old boy with humeroradial synostosis, elbow flexion contractures, pre‐ and postnatal growth retardation and facial dysmorphism caused by a novel homozygous splice site variant in ESCO2 .…”

Section: Introductionmentioning

confidence: 99%

Roberts syndrome in an Indian patient with humeroradial synostosis, congenital elbow contractures and a novel homozygous splice variant in ESCO2

Schneeberger

Nayak

Fuchs

et al. 2020

American J of Med Genetics Pt A

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Roberts syndrome (also known as Roberts-SC phocomelia syndrome) is an autosomal recessive developmental disorder, characterized by pre-and postnatal growth retardation, limb malformations including bilateral symmetric tetraphocomelia or mesomelia, and craniofacial dysmorphism. Biallelic loss-of-function variants in ESCO2, which codes for establishment of sister chromatid cohesion N-acetyltransferase 2, cause Roberts syndrome. Phenotypic spectrum among patients is broad, challenging clinical diagnosis in mildly affected individuals. Here we report a 3-year-old boy with a mild phenotype of Roberts syndrome with bilateral elbow contractures, humeroradial synostosis, mild lower limb disparity, and facial dysmorphism. Trio whole-exome sequencing identified the novel biallelic splice variant c.1673+1G>A in ESCO2 in the patient. Aberrant ESCO2 pre-mRNA splicing, reduced relative ESCO2 mRNA amount, and characteristic cytogenetic defects, such as premature centromere separation, heterochromatin repulsion, and chromosome breaks, in patient cells strongly supported pathogenicity of the ESCO2 variant affecting one of the highly conserved guanine-thymine dinucleotide of the donor splice site. Our case highlights the difficulty in establishing a clinical diagnosis in individuals with minor clinical features of Roberts syndrome and normal intellectual and social development. However, next-generation sequencing tools allow for molecular diagnosis in cases presenting with mild developmental defects.

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Section: Introductionmentioning

confidence: 99%

Roberts syndrome in an Indian patient with humeroradial synostosis, congenital elbow contractures and a novel homozygous splice variant in ESCO2

Schneeberger

Nayak

Fuchs

et al. 2020

American J of Med Genetics Pt A

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“…In addition to these anomalies, random chromosomal loses and sporadic aneuploidies involving different chromosomes can be seen related with early centromere segregation. [11,13] However, normal karyotype is seen in some of the cases reported in the literature. The mutation in ESCO2 gene coding the protein which conducts the acetyl transferase activity necessary for the attachment of sister chromatids during S phase to each other is responsible for this syndrome.…”

Section: Discussionmentioning

confidence: 98%

A case of Roberts syndrome: its ultrasonographic characteristics and genetic diagnosis

Ayaz¹,

Göktaş²,

Balasar³

2020

Perinatal J

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Objective: Roberts syndrome is a very rare genetic disease, and it has an autosomal recessive inheritance pattern. It develops as a result of the mutation in ESCO2 gene located in the 8th chromosome. In our study, we aimed to present a case which was found to have Roberts syndrome coexisting with multiple anomalies, particularly skeletal system anomaly, in the 17 weeks of gestation. Case(s): In the fetal ultrasonographic evaluation performed on the pregnant women who referred to our hospital for routine gestational examination in the 17 weeks of gestation, anomalies in the bilateral upper and lower extremities, contracted legs, bilateral cleft palate and lip, intrauterine growth restriction and cardiac anomaly were found in the fetus. Roberts syndrome was considered first with these ultrasonographic findings. The diagnosis of Roberts syndrome was confirmed by cytogenetic and molecular analyses. Early segregation of centromeres and early breaking up of heterochromatic regions near centromeres were found at metaphase stage. By cytogenetic and molecular analyses, homozygous mutation in ESCO2 gene of the fetus and heterozygous mutation in the parents were found. The termination of pregnancy was decided after the genetic consultation with the parents. Physical examination findings and prenatal ultrasound findings after termination were found similar. Conclusion: Many severe skeletal dysplasia cases can be diagnosed ultrasonographically before 20 weeks of gestation. Early diagnosis ensures to take necessary actions for medical support during postnatal period and in terms of labor if pregnancy continues as well as genetic consultation opportunity. If the genetic disease that causes skeletal dysplasia can be identified and parents are found to have this gene, healthy pregnancies can be achieved by obtaining normal embryos via pre-implantation genetic diagnosis in order to prevent the relapse of the disease.

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“…However, individuals that are mildly affected sometimes grow into adulthood. 13 , 14 Other associations include abnormalities of the heart—atrial septal defect, ventricular septal defect, and patent ductus arteriosus. They also present with polycystic or horseshoe kidneys.…”

Section: Discussionmentioning

confidence: 99%

“…Mildly affected individuals may live into adulthood. 13 , 14 Roberts-SC phocomelia represents the milder form of Roberts syndrome and typically survive to adulthood. 13 The majority of infants with Roberts syndrome die due to cardiac, renal anomalies, and neonatal infective complications.…”

Section: Introductionmentioning

confidence: 99%

Roberts syndrome with tetraphocomelia: A case report and literature review

Okpala

Echendu²,

Ikechebelu

et al. 2022

SAGE Open Medical Case Reports

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Roberts syndrome is a rare genetic disorder characterized by symmetrical reductive limb malformation and craniofacial abnormalities. It is caused by mutation in the “Establishment of cohesion 1 homolog 2” genes, resulting in the loss of acetyltransferase activities and manifesting as premature centromere separation in metaphase chromosomes. The affected individual grows slowly during pregnancy and after birth with associated mild to severe intellectual impairment. We present a 35-year-old multiparous Nigerian lady who had emergency cesarean section at 35 weeks of gestation following abruptio placentae with a live fetus. The baby had poor Apgar score at birth and died shortly afterward. Tetraphocomelia was detected on prenatal ultrasound done at about 24 weeks of gestation with other features sonographically normal. However, clinical diagnosis of severe variant of Roberts syndrome with tetraphocomelia, growth restriction, and craniofacial abnormalities were noted at birth. This case exhibits a very rare variant of Roberts syndrome with tetraphocomelia, intrauterine growth restriction, and craniofacial abnormalities. It also highlights the crucial role of detailed clinical examination and the inherent challenges in making cytogenetic diagnosis in low-income countries.

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Hypopigmented patches in Roberts/SC phocomelia syndrome occur via aneuploidy susceptibility

Cited by 8 publications

References 22 publications

Roberts syndrome in an Indian patient with humeroradial synostosis, congenital elbow contractures and a novel homozygous splice variant in ESCO2

Roberts syndrome in an Indian patient with humeroradial synostosis, congenital elbow contractures and a novel homozygous splice variant in ESCO2

A case of Roberts syndrome: its ultrasonographic characteristics and genetic diagnosis

Roberts syndrome with tetraphocomelia: A case report and literature review

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