A case of de Barsy syndrome with a severe eye phenotype

Al‐Owain, Mohammed; Al-Anazi, Shamsa; Khalifa, Ola; Al-Hemidan, Amal; Al-Ebdi, Loai; Al‐Saud, Bandar; Alkuraya, Fowzan S.

doi:10.1002/ajmg.a.35507

Cited by 5 publications

(3 citation statements)

References 11 publications

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“…Out of the 42 genes highlighted in this cohort, 13 were associated with specific OMIM phenotypes that lack DSD ( (Alazami et al, 2016;Al-Owain et al, 2012). However, the diagnosis of polycystic kidney disease is recent and was not included in the previously published description.…”

Section: Genes With Assigned Omim Phenotypes That Do Not Include Dsdmentioning

confidence: 99%

Survey of disorders of sex development in a large cohort of patients with diverse Mendelian phenotypes

Abualsaud

Hashem

Alhashem

et al. 2020

American J of Med Genetics Pt A

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Disorders of sex development (DSD) are congenital conditions with atypical development of chromosomal, gonadal, or anatomical sex. The estimated incidence ranges from 1 in 4,500-5,500 for strictly defined "ambiguous genitalia" to 1 in 300 or higher when a broader definition is implemented. In this study, we aim to define DSD phenotypes encountered in a large heterogeneous cohort of molecularly characterized Mendelian disorders in a single center. Data were retrieved for patients with documented abnormal genitalia based on the 2006 consensus criteria. Out of 149 patients (129 families) with compatible human phenotype ontology, 76 patients (68 families) had an identified genetic cause and were included in our analysis. Potentially causal variants were identified in 42 genes, and two patients had a dual molecular diagnosis. Six genes have no associated phenotype in OMIM (PIANP, CELSR2, USP2, FAM179B, TXNDC15, and CCDC96). Thirteen genes have non-DSD OMIM phenotypes, thus we are expanding their phenotype to include DSD. We also highlight how certain disorders are under-recognized despite their established DSD phenotype in OMIM, especially CTU2-related DREAM-PL syndrome and TSPYL1-related sudden infant death with dysgenesis of the testes syndrome. In conclusion, this study of a large heterogeneous Mendelian cohort expands the list of genes and disorders beyond those classically DSD-linked. K E Y W O R D S ambiguous genitalia, differences in sex development, sex reversal 1 | INTRODUCTION Disorders of sex development (DSD) are defined as congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical (Lee et al., 2016). The clinical phenotypes of these disorders are heterogenous and include micropenis, cryptorchidism, clitoromegaly and, in more severe cases, ambiguous genitalia. The exact incidence can be challenging to determine accurately due to discrepancy in the definition used by the different epidemiological studies and the changes in classification over time. However, it is estimated to be 1 in 4,500-5,500 for strictly defined "ambiguous genitalia" and increases to 1 in 300 or higher if a broader definition is used (

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Section: Genes With Assigned Omim Phenotypes That Do Not Include Dsdmentioning

confidence: 99%

Survey of disorders of sex development in a large cohort of patients with diverse Mendelian phenotypes

Abualsaud

Hashem

Alhashem

et al. 2020

American J of Med Genetics Pt A

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“…De Barsy syndrome is a rare genetic syndrome characterized by cutis laxa III (ARCL3 OMIM# 219150, 614438), progeroid appearance, ophthalmic opacification, skeletal malformations, growth delays, and intellectual disability . Given the diverse array of ophthalmic and skeletal malformations, de Barsy patients require frequent surgical interventions . First described by de Barsy in 1967, only 100 cases of the syndrome have been documented in the medical literature.…”

Section: Introductionmentioning

confidence: 99%

“…The constellation of clinical manifestations of de Barsy syndrome include intrauterine growth retardation, postnatal growth delay, motor delay, cognitive impairment, hypotonia, athetoid movements, microcephaly, wormian bones, large fontanelles, facial dysmorphism, cataracts, corneal clouding, thin/wrinkled skin, easy bruising, sparse hair, joint laxity, osteopenia, and inguinal hernias . A number of de Barsy syndrome manifestations are directly relevant to perioperative patient management .…”

Section: Introductionmentioning

confidence: 99%

Clinical implications of de Barsy syndrome

Warner

Olsen

Smith

2017

Pediatric Anesthesia

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Summary Background De Barsy syndrome is a rare, autosomal recessive syndrome characterized by cutis laxa, progeroid appearance, ophthalmic opacification, skeletal malformations, growth delays, and intellectual disability. Aims The aim of this case series is to identify the anesthetic considerations in the clinical management of patients with de Barsy syndrome. Methods A retrospective case review from 1968 to 2016 was performed at a single tertiary medical center to identify patients with de Barsy syndrome who underwent anesthesia for diagnostic and surgical procedures. We collected and analyzed the perioperative records and following data: age, sex, American Society of Anesthesiologists physical status, relevant comorbidities, surgical procedures, anesthesia management, and observed complications. Results Three patients underwent 64 unique anesthetics for a diverse collection of diagnostic and surgical procedures. An array of anesthetics and techniques were successfully used. Observations of the perioperative period found 7 episodes of intraoperative hyperthermia (>38.3°), a single difficult airway requiring fiberoptic bronchoscopic‐guided intubation, and repeatedly difficult intravenous access. Conclusion This expanded case series suggests that providers caring for patients with de Barsy syndrome should be aware of potential challenges with airway management, vascular access, and temperature monitoring.

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Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue

et al. 2016

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Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the connective tissue, primarily that of the skin, joint and vessels, is abnormal, although the resulting clinical manifestations can vary widely between the different historical subtypes. Many cases of hereditary disorders of connective tissue that do not seem to fit these historical subtypes exist. The aim of this study is to describe a large series of patients with inherited connective tissue disorders evaluated by our clinical genetics service and for whom a likely causal variant was identified. In addition to clinical phenotyping, patients underwent various genetic tests including molecular karyotyping, candidate gene analysis, autozygome analysis, and whole-exome and whole-genome sequencing as appropriate. We describe a cohort of 69 individuals representing 40 families, all referred because of suspicion of an inherited connective tissue disorder by their primary physician. Molecular lesions included variants in the previously published disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and SPARC with interesting variations on the published clinical phenotypes. We also describe the first recessive EDS-like condition to be caused by a recessive COL1A1 variant. In addition, exome capture in a familial case identified a homozygous truncating variant in a novel and compelling candidate gene, AEBP1. Finally, we also describe a distinct novel clinical syndrome of cutis laxa and marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome sequencing of the two families with this new clinical entity. Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome.

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A case of de Barsy syndrome with a severe eye phenotype

Cited by 5 publications

References 11 publications

Survey of disorders of sex development in a large cohort of patients with diverse Mendelian phenotypes

Survey of disorders of sex development in a large cohort of patients with diverse Mendelian phenotypes

Clinical implications of de Barsy syndrome

Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue

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