Tracheomalacia in siblings with otopalatodigital syndrome

Johnson, Jonathan N.; Hartman, Tyler; Krych, Esther H.; Seferian, Edward G.; Ouellette, Yves

doi:10.1002/ajmg.a.32263

Cited by 3 publications

(2 citation statements)

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“…Respiratory failure due to thoracic hypoplasia is also known to be a cause of early death. Up to now, only two cases of tracheomalacia have been reported in OPD2 3 . We encountered a male infant with OPD2 with unusual clinical findings including congenital retinal folds, optic nerve hypoplasia, and tracheomalacia.…”

Section: Figmentioning

confidence: 94%

Retinal folds and tracheomalacia in a boy with otopalatodigital syndrome type 2

Okuno

Igarashi

Sugihara

et al. 2022

Pediatrics International

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Section: Figmentioning

confidence: 94%

Retinal folds and tracheomalacia in a boy with otopalatodigital syndrome type 2

Okuno

Igarashi

Sugihara

et al. 2022

Pediatrics International

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“…This is also confounded by the overlap of the location of substitutions in FLNA that lead to OPD1 or OPD2 in males (Moutton et al, 2016; Robertson, 2005). Occasionally, a female individual may manifest more severely with OPD2 and present similarly to males, presumably on account of a lack of skewed X‐inactivation that usually favors expression of the nonmutant bearing allele (Johnson, Hartman, Krych, Seferian, & Ouellette, 2008; Robertson et al, 2001).…”

Section: Gain‐of‐function Flna Disordersmentioning

confidence: 99%

The X‐linked filaminopathies: Synergistic insights from clinical and molecular analysis

et al. 2020

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The X-linked filaminopathies represent a diverse group of clinical conditions, all caused by variants in the gene FLNA. FLNA encodes the widely expressed actin binding protein, filamin A that has multiple roles during embryonic development including cell migration, mechanical sensing, and cell signaling. In this review, we discuss the 10 distinct X-linked filaminopathy conditions that between them affect almost all organ systems, including the brain, skeleton, heart, and skin, highlighting the critical role of this protein in human development. We review each of the phenotypes and discuss their pathogenesis, where known. Assigning pathogenicity to variants in FLNA can prove difficult, especially for missense variants and small indels, in-part because of the X-linked nature of the phenotypes, the overlap of phenotypic features between conditions, and poor understanding of the function of certain protein domains. We outline here approaches to characterize phenotypes, highlight hotspot regions within FLNA commonly mutated in these conditions, and approaches to resolving some variants of uncertain significance. K E Y W O R D S filamin A, filaminopathy, periventricular nodular heterotopia, skeletal dysplasia, X-linked disease 1 | INTRODUCTION Pathogenic variants in FLNA, the X-linked gene that encodes the cytoskeletal protein filamin A (FLNA), cause a diverse spectrum of genetic syndromes with features ranging from impaired brain development to skeletal dysplasias, gastrointestinal disorders, and compromised structure and function of the cardiac valves. To date, eight discrete syndromes are formally associated with variants in FLNA reported in OMIM (MIM# 300017). These are X-linked cardiac valvular dysplasia, congenital short bowel syndrome (also called X-linked congenital idiopathic intestinal pseudo-obstruction), frontometaphyseal dysplasia type I, periventricular nodular heterotopia (PH), Melnick -needles syndrome (MNS), otopalatodigital syndrome type 1 (OPD1), OPD2, and digitocutaneous dysplasia (DCD; formally terminal osseous dysplasia). At least two more entities should be added to this list, isolated thrombocytopenia (Nurden et al., 2011) and a disorder characterized by keloid scarring, joint contractures, and cardiac valvulopathy (Atwal et al., 2016; Lah et al., 2015). Collectively, these conditions have been termed the X-linked filaminopathies.The broad diversity of organ systems affected across this phenotypic spectrum highlight the pivotal role that FLNA plays in human development and its widespread, but not quite ubiquitous, expression (Fox et al., 1998;Robertson et al., 2003Robertson et al., , 2007. Additionally, due to the X chromosomal location of FLNA, the presentation of FLNArelated phenotypes varies between males and females. These factors conspire to make the clinical and molecular diagnosis of FLNA-related disorders challenging.Here, we review the phenotypes associated with mutations in FLNA with emphasis on those that have been newly described since the previous comprehensive review on filaminopat...

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Síndrome otopalatodigital tipo II, aproximación prenatal y diagnóstico clínico de un caso complejo de displasia ósea

Saldarriaga

Nieto-Calvache

Quintero

et al. 2012

Rev. chil. obstet. ginecol.

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RESUMENEl síndrome otopalatodigital tipo 2 (OPD2), es una rara entidad con herencia recesiva ligada al cromosoma X, letal, caracterizada por facies anormales con hipoplasia centrofacial, hipertelorismo ocular, paladar hendido, talla baja, huesos largos curvos, sindactilia en pies y manos y anomalías óseas. Usualmente originadas en mutaciones en el gen de la filamina A (FLNA). Se reporta un caso, con diagnóstico prenatal de osteocondrodisplasia que posteriormente por hallazgos al examen físico y radiológicos del recién nacido se clasifico como síndrome otopalatodigital tipo 2.PALABRAS CLAVE: Genética, osteocondrodisplasias, diagnóstico prenatal, anomalías músculo esqueléticas SUMMARYOtopalatodigital syndrome, type 2 (OPD2), is a rare entity with recessive heredity linked to the X chromosome, lethal, characterized by abnormal facies, with centro-facial hypoplasia, ocular hypertelorism, cleft palate, low height, curved long bones, syndactyly, and osseous anomalies on feet and hands. It has been recently shown that patients with OPD2 with mutations in the filamin A gene (FLNA), which is also found altered in allelic entities like the OPD1 syndrome, the Melnik-Needles syndrome and frontometaphyseal dysplasia. Herein, we report a case with prenatal osteochondrodysplasia diagnosis that after physical and radiological exam of the newborn was classified as otopalatodigital syndrome type 2.KEY WORDS: Genetics, osteochondrodysplasias, prenatal diagnosis, musculoskeletal abnormalities INTRODUCCIÓNEl síndrome de otopalatodigital, tipo 2 (OMIM OPD2: # 304120) es una rara entidad letal, con herencia recesiva ligada al cromosoma X, caracterizada por facies anormales con hipoplasia facial central, hipertelorismo ocular, paladar hendido, talla baja, huesos largos curvos, sindactilia, y anomalías óseas en pies y manos. Otros hallazgos menos frecuentes abarcan onfalocele, defectos renales de las vías urinarias. El fallecimiento suele ser perinatal, algunos pacientes solo alcanzan pocos meses de vida (1,2,3). Recientemente se ha demostrado que los pacientes con OPD 2 tienen mutaciones en el gen A filamina (FLNA), que también se encuentra alterado en entidades alélicas como el síndrome

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Tracheomalacia in siblings with otopalatodigital syndrome

Cited by 3 publications

References 14 publications

Retinal folds and tracheomalacia in a boy with otopalatodigital syndrome type 2

Retinal folds and tracheomalacia in a boy with otopalatodigital syndrome type 2

The X‐linked filaminopathies: Synergistic insights from clinical and molecular analysis

Síndrome otopalatodigital tipo II, aproximación prenatal y diagnóstico clínico de un caso complejo de displasia ósea

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