Case Report: Blepharophimosis and Ptosis as Leading Dysmorphic Features of Rare Congenital Malformation Syndrome With Developmental Delay – New Cases With TRAF7 Variants

Paprocka, Justyna; Nowak, Magdalena; Nieć, Maria; Janik, Izabela; Rydzanicz, Małgorzata; Robert, Śmigiel; Kłaniewska, Magdalena; Rutkowska, Karolina; Płoski, Rafał; Jezela‐Stanek, Aleksandra

doi:10.3389/fmed.2021.708717

Cited by 7 publications

(12 citation statements)

References 23 publications

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“…Bouwmeester et al (2004) found that homodimerization of TRAF7 occurs at the central TRAF and CC domains whereas its WD40 repeats bind MEKK3, a mouse homolog for mitogen‐activated protein kinase kinase kinase 3 (MAP3K3). Notably, most somatic and germline variants are identified in this WD40 domain (Castilla‐Vallmanya et al, 2020; Paprocka et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Novel mosaic TRAF7 likely pathogenic variant in an African American family

Colleran

Daykin

Hernandez

et al. 2023

American J of Med Genetics Pt A

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Pathogenic variants in TRAF7 are often de novo and features of individuals harboring these variants are characterized by neurodevelopmental delay, ptosis, cardiac defects, limb anomalies, and dysmorphic features. We present a familial case in two African American patients with a novel, likely pathogenic c.1936G>A variant in TRAF7. Patient 1 is a 31-year-old female with a patent ductus arteriosus (PDA), intellectual disability, ptosis, and other dysmorphic features. She was identified to harbor this likely pathogenic variant in a mosaic (33.89%) state in leukocytes. Her son, Patient 2, is a 10-month-old male with a PDA, atrial septal defect, ptosis, developmental delay, history of feeding difficulties, congenital maxillary frenulum, and malrotation of the intestine. He has the same variant in a non-mosaic state. These cases demonstrate the variable expressivity observed with variants in TRAF7 within the same family and expand upon current understanding of mosaic TRAF7 variants. They also provide phenotypic data on genetic variation in individuals with African American ancestry, a population who has been underrepresented in the literature and may be less frequently referred to genetic specialists.

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Section: Introductionmentioning

confidence: 99%

Novel mosaic TRAF7 likely pathogenic variant in an African American family

Colleran

Daykin

Hernandez

et al. 2023

American J of Med Genetics Pt A

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“…The phenotypic spectrum of this condition can include congenital heart defects, digital abnormalities, dysmorphic facial features, micro and macrocephaly, renal anomalies, intellectual disability, seizures, and hearing loss. 2,3 All previous reports of affected individuals are children and adults. To our knowledge, a prenatal diagnosis of this condition has not yet been reported.…”

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confidence: 99%

Prenatal diagnosis of a germline variant in TRAF7: Importance of accessibility to prenatal exome sequencing in cases of structural fetal anomalies

2022

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“…All variants were confirmed to have occurred de novo , except for P1, conceived by ovodonation, for whom the paternal sample was negative. Eight different variants have been detected (Table 3), seven of them previously associated with TRAF7 syndrome [1,2,5,7] including the recurrent variant p.Arg655Gln, which was detected in four unrelated patients (Patients 8 to 11). Patient 7 harbors a novel variant, c.1958G>T, p.(Arg653Leu), in a residue where other amino acid substitutions have been previously reported in meningiomas [25].…”

Section: Resultsmentioning

confidence: 99%

“…This apparent division where some missense changes in germline lead to TRAF7 patients migth be due to a correlation in the pathomechanisms of both RASopathies and TRAF7 syndrome involving the regulation of RAS/MAPK signaling pathways [1,5].…”

Section: Discussionmentioning

confidence: 99%

“…Since its initial description in 2018 [1] and further delineation [2], a total of 58 subjects with TRAF7 syndrome have been published, carrying 26 different variants [3][4][5][6][7][8]. While the clinical presentation of the syndrome appears to be highly variable, some common features have been identified, including a range of neurological and developmental abnormalities, such as intellectual disability, speech and language delays, and motor impairments, as well as epilepsy in some individuals.…”

Section: Introductionmentioning

confidence: 99%

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Expanding the phenotypic spectrum of TRAF7 syndrome: report of eleven new cases and literature review

Palma-Milla,

Prat-Planas,

Soengas-Gonda

et al. 2023

Preprint

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TRAF7 syndrome, a multisystemic neurodevelopmental disorder caused by germline missense variants in theTRAF7gene, exhibits heterogeneous clinical presentations. We present a detailed description of eleven new TRAF7 syndrome cases, featuring eight distinct variants, including a novel one. Phenotypic analysis and a comprehensive review of the 58 previously reported cases outline consistent clinical presentations, emphasizing dysmorphic features, developmental delay, endocrine manifestations, and cardiac defects. In this enlarged collection, novelties include a wider range of cognitive dysfunction, with some individuals exhibiting normal development despite early psychomotor delay. Communication challenges, particularly in expressive language, are prevalent, necessitating alternative communication methods. Autistic traits, notably rigidity, are observed in the cohort. Also, worth highlighting are hearing loss, sleep disturbances, and endocrine anomalies, including growth deficiency. Cardiac defects, frequently severe, pose early-life complications. Facial features, including arched eyebrows, contribute to the distinct gestalt. A novel missense variant, p.(Arg653Leu), further underscores the complex relationship between germlineTRAF7variants and somatic changes linked to meningiomas. Our comprehensive analysis expands the phenotypic spectrum, emphasizing the need for oncological evaluations and proposing an evidence-based schedule for clinical management. This study contributes to a better understanding of TRAF7 syndrome, offering insights for improved diagnosis, intervention, and patient care.Key MessageTRAF7 syndrome, a complex neurodevelopmental disorder, exhibits variable cognitive outcomes, complex behavioral presentation and clinical complications emphasizing the need for tailored interventions and follow-up.

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Case Report: Blepharophimosis and Ptosis as Leading Dysmorphic Features of Rare Congenital Malformation Syndrome With Developmental Delay – New Cases With TRAF7 Variants

Cited by 7 publications

References 23 publications

Novel mosaic TRAF7 likely pathogenic variant in an African American family

Novel mosaic TRAF7 likely pathogenic variant in an African American family

Prenatal diagnosis of a germline variant in TRAF7: Importance of accessibility to prenatal exome sequencing in cases of structural fetal anomalies

Expanding the phenotypic spectrum of TRAF7 syndrome: report of eleven new cases and literature review

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