Cardiovascular malformations in Fryns syndrome: Is there a pathogenic role for neural crest cells?

Lin, Angela E.; Pober, Barbara R.; Mullen, Mary P.; Slavotinek, Anne

doi:10.1002/ajmg.a.31023

Cited by 41 publications

(42 citation statements)

References 68 publications

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“…22 Of note, a pathogenic role for neural crest cells was also suspected for Lujan-Fryns Syndrome with the involvement of MED12, another member of the Mediator complex. 23 In addition, MED13L and other subunits of the Mediator complex were recently shown to have a role in Rb/E2F-induced growth inhibition. 24 So far, no increased tumor susceptibility was observed in patients with MED13L defects, however, that may be due to the limited number of patients known and their young age.…”

Section: Discussionmentioning

confidence: 99%

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Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability

Asadollahi

Oneda

Sheth³

et al. 2013

Eur J Hum Genet

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A chromosomal balanced translocation disrupting the MED13L (Mediator complex subunit13-like) gene, encoding a subunit of the Mediator complex, was previously associated with transposition of the great arteries (TGA) and intellectual disability (ID), and led to the identification of missense mutations in three patients with isolated TGA. Recently, a homozygous missense mutation in MED13L was found in two siblings with non-syndromic ID from a consanguineous family. Here, we describe for the first time, three patients with copy number changes affecting MED13L and delineate a recognizable MED13L haploinsufficiency syndrome. Using high resolution molecular karyotyping, we identified two intragenic de novo frameshift deletions, likely resulting in haploinsufficiency, in two patients with a similar phenotype of hypotonia, moderate ID, conotruncal heart defect and facial anomalies. In both, Sanger sequencing of MED13L did not reveal any pathogenic mutation and exome sequencing in one patient showed no evidence for a non-allelic second hit. A further patient with hypotonia, learning difficulties and perimembranous VSD showed a 1 Mb de novo triplication in 12q24.2, including MED13L and MAP1LC3B2. Our findings show that MED13L haploinsufficiency in contrast to the previously observed missense mutations cause a distinct syndromic phenotype. Additionally, a MED13L copy number gain results in a milder phenotype. The clinical features suggesting a neurocristopathy may be explained by animal model studies indicating involvement of the Mediator complex subunit 13 in neural crest induction.

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Section: Discussionmentioning

confidence: 99%

“…The third patient is a girl born 5 days preterm with a history of transient but marked fetal hydrops during pregnancy (weeks [16][17][18][19][20][21][22][23][24][25]. Her birth weight was 2200 g (o3rd centile) and the length was 47 cm (3rd centile).…”

Section: Patientmentioning

confidence: 99%

Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability

Asadollahi

Oneda

Sheth³

et al. 2013

Eur J Hum Genet

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“…The six diagnostic criteria for Fryns Syndrome are as follows: 1) diaphragmatic defect, 2) characteristic facial appearance, 3) distal digital hypoplasia, 4) pulmonary hypoplasia, 5) characteristic associated anomalies like polyhydramnios, brain malformations, renal dysplasia, gastrointestinal system malformations and genital malformations and 6) Parental consanguinity (Lin et al, 2005). At least three findings should be present for Fryns syndrome but in the present case all six criteria were present.…”

Section: Discussionmentioning

confidence: 67%

Fryns Syndrome in Monozygotic Twins: A Case Report with Review of Literature

2012

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SUMMARY:Fryns syndrome is a rare multiple congenital anomaly syndrome. The syndrome is characterized by congenital diaphragmatic hernia, unusual facial features and distal limb abnormalities. Here we report a case of monozygotic twins with Fryns syndrome of consanguine parents with normal first child. The mother with 20 weeks of gestation having hyperemesis was referred from a primary health centre to the department of obstetrics and gynaecology at our hospital with polyhydramnios detected in ultrasonogram. Detailed ultrasound was done and after finding that both babies having multiple congenital anomalies, emergency caeserian section was done. The malformations in the twins suggestive of Fryns syndrome.

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“…The most common manifestations of FS are diaphragmatic hernia (60-96%), pulmonary hypoplasia (65%), nail hypoplasia (59%), hypoplasia of the distal phalanges (59%), polyhydramnios (56%), craniofacial dysmorphism with cleft palate (50-70%), and ventricular septal defect (40-55%) [3][4][5] . Except for nail hypoplasia, most of these anomalies can be detected easily via sonography.…”

Section: Discussionmentioning

confidence: 99%

Fryns syndrome: Case report and review of the literature

Yücesoy

Çakıroğlu

Çalışkan

2007

J of Clinical Ultrasound

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Fryns syndrome (FS) is a rare malformation. We report a case of FS referred to our clinic at 27 weeks' gestation with a diagnosis of congenital diaphragmatic hernia. Sonographic examination of the fetus revealed a left-sided diaphragmatic hernia, pulmonary hypoplasia, and a median orofacial cleft. The diagnosis of FS was made after exclusion of chromosome aberrations and delivery of the fetus. Macroscopic inspection revealed a coarse face (hypertelorism and broad and flat nasal bridge, anteverted nostrils, median cleft lip/palate, poorly shaped auricles with attached earlobes, facial hirsutism), a narrow thorax, nail hypoplasia, and hypoplastic, widely spaced nipples.

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Cardiovascular malformations in Fryns syndrome: Is there a pathogenic role for neural crest cells?

Cited by 41 publications

References 68 publications

Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability

Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability

Fryns Syndrome in Monozygotic Twins: A Case Report with Review of Literature

Fryns syndrome: Case report and review of the literature

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