Silver-Russell Syndrome and Beckwith-Wiedemann Syndrome: Opposite Phenotypes with Heterogeneous Molecular Etiology

Abstract

Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS) are 2 clinically opposite growth-affecting disorders belonging to the group of congenital imprinting disorders. The expression of both syndromes usually depends on the parental origin of the chromosome in which the imprinted genes reside. SRS is characterized by severe intrauterine and postnatal growth retardation with various additional clinical features such as hemihypertrophy, relative macrocephaly, fifth finger clinodactyly, and triangular facies. BWS is an overgrowth syndrome with many additional clinical features such as macroglossia, organomegaly, and an increased risk of childhood tumors. Both SRS and BWS are clinically and genetically heterogeneous, and for clinical diagnosis, different diagnostic scoring systems have been developed. Six diagnostic scoring systems for SRS and 4 for BWS have been previously published. However, neither syndrome has common consensus diagnostic criteria yet. Most cases of SRS and BWS are associated with opposite epigenetic or genetic abnormalities in the 11p15 chromosomal region leading to opposite imbalances in the expression of imprinted genes. SRS is also caused by maternal uniparental disomy 7, which is usually identified in 5-10% of the cases, and is therefore the first imprinting disorder that affects 2 different chromosomes. In this review, we describe in detail the clinical diagnostic criteria and scoring systems as well as molecular causes in both SRS and BWS.

MANAGEMENT OF ENDOCRINE DISEASE: Diagnostic and therapeutic approach of tall stature

“…The most common features are macroglossia, abdominal wall defects and neonatal hypoglycemia due to islet cell hyperplasia (52,53). Newborns are macrosomic and children grow parallel or above the 95th percentile until around 8 years, with a fall in growth velocity after that.…”

Pushes and pulls from below: Anatomical variation, articulation and sound change

“…These may be part of wider syndromes or occur isolated, and they helped shed light on genes involved in the development of the vocal tract (Dixon et al 2011;Bush & Jiang 2012;Setó-Salvia & Stanier 2014). Much less well studied are pathologies affecting the tongue (such as micro-, macro-and ankylo-glossia; Reynoso et al 1994;Hong 2013;Ounap 2016), the velum or the larynx (e.g., cleft larynx; Johnston et al 2014). While probably less directly relevant to sound change than normal variation, such pathologies, coupled with animal models and evolutionary-developmental studies (Jernvall & Thesleff 2012), open the door to understanding the genetic and developmental mechanisms involved in the emergence of the observed patterns of variation between normal individuals.…”

Investigação genético-molecular em pacientes com alta estatura

“…Although two studies showed only about 7% of dissatisfaction in treated patients, the largest one, comprising around 400 women in each treated and untreated groups, has shown that 99.1% of untreated and 57.9% of treated women were satisfied with this decision. The dissatisfaction in the treated group was mostly not related to the achieved adult height, but was instead caused by the small difference between actual and predicted adult height, by side effects during the treatment or concerns about its long-term consequences and by the lack of participation in the decision process of whether to be treated or not (87).…”

“…Few studies assessed satisfaction with sex steroid treatment retrospectively (76,78,87). Although two studies showed only about 7% of dissatisfaction in treated patients, the largest one, comprising around 400 women in each treated and untreated groups, has shown that 99.1% of untreated and 57.9% of treated women were satisfied with this decision.…”

“…As alterações responsáveis ___________________________________________________________________ pelo surgimento da síndrome se encontram no braço curto do cromossomo 11, na região 11p15. Essa região normalmente sofre o fenômeno de silenciamento (ou imprinting), com a expressão dos genes IGF2 e KCNQ1OT1 pelo alelo paterno, com hipermetilação da região IC1 (imprinting center 1), e a expressão dos genes KCNQ1 e CDKC1C pelo alelo materno, com hipermetilação da região IC2 (imprinting center 2)86 .As alterações descritas como causadoras da síndrome consistem em perda da metilação da região IC2 em 50% dos casos, ganho de metilação na região IC1 em 5-10%, dissomia uniparental paterna em 20% e mutações no gene CDKN1C em 5% dos casos esporádicos85,87 . Cerca de 20% dos pacientes permanece sem diagnóstico molecular de pilar para a formação das fibras elásticas, como as presentes na parede da aorta, além de formar a microarquitetura de estruturas sem fibras elásticas, como o ligamento suspensório do cristalino88 .…”