Report of a patient with Temple–Baraitser syndrome

Yeşil, Gözde; Güler, Serhat; Yüksel, Adnan; Alanay, Yasemin

doi:10.1002/ajmg.a.36344

Cited by 9 publications

(4 citation statements)

References 6 publications

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“…e Patient at age 4 years 4 months reported in [ 18 ] (with permission from Springer Nature). f Patient at age 3 years 7 months reported in [ 49 ] (with permission from John Wiley and Sons). g Patient at age 6 years reported in [ 17 ] (with permission from Springer Nature).…”

Section: Methodsmentioning

confidence: 99%

Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3—a subgroup of K+ channelopathies

et al. 2021

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Decreased or increased activity of potassium channels caused by loss-of-function and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human disorders affecting the central nervous system, heart, kidney, and other organs. While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K+ channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann–Laband and Temple–Baraitser syndromes, caused by dominant variants in KCNH1, FHEIG syndrome due to dominant variants in KCNK4, and the clinical picture associated with dominant variants in KCNN3. Here we review the presentation of these individuals, including five newly reported with variants in KCNH1 and three additional individuals with KCNN3 variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant KCNN3, KCNH1, and KCNK4 variants, sharing developmental delay and/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K+ conductance, referred to as syndromic neurodevelopmental K+ channelopathies due to dominant variants in KCNH1, KCNK4, or KCNN3.

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Section: Methodsmentioning

confidence: 99%

Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3—a subgroup of K+ channelopathies

et al. 2021

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“…Temple–Baraitser syndrome (TBS, OMIM #611816) was first described in 1991, with the main distinguishing feature being the appearance of the thumbs and great toes ( Temple and Baraitser, 1991 ). Each of the four cases subsequently reported showed consistent findings of severe developmental delay and characteristic craniofacial dysmorphisms and seizures, in addition to the pollex and hallux abnormalities ( Gabbett et al , 2008 ; Jacquinet et al , 2010 ; Yesil et al , 2014 ). The thumbs are broad and the great toes are elongated, with the nails either hypoplastic or completely absent.…”

Section: Introductionmentioning

confidence: 68%

Two cases of Temple–Baraitser syndrome

Shen

2015

Clinical Dysmorphology

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This study reports on two individuals with Temple–Baraitser syndrome, manifesting typical hallux and pollex findings, global developmental delay, and seizures. In the five previous cases identified to date, consistent craniofacial and osseous characteristics have been observed. The children described herein exhibit minor differences within this phenotype and are older, highlighting the phenotypic variability and natural history of the clinical and radiographic findings.

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“…Using the SFARI Gene database, we screened nine candidate ASD-risk genes which have seldom been reported as associated with ASD: seven candidate ASD-risk genes related to SNVs in Class 4 ( CUL4B , KCNH1 , PLA2G6 , SLC16A2 , SSR4 , UFC1 , and WFS1 ) (Table 4 ), and two candidate dosage-sensitive genes related to ASD-causing CNVs in the “recorded CNVs without ASD-risk genes” group ( ELN and GJA5 ) (Table 5 ). Of the genes in Class 4, CUL4B , KCNH1 , and PLA2G6 have been reported to cause a phenotype of ASD or ASD-like behavior in several cases [ 43 , 56 , 57 ]. Additionally, WFS1 is reported to be closely associated with multiple psychiatric illnesses, including severe depression, psychosis, obsessive-compulsive disorder, and suicidal behavior [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing

Wu,

Li,

Meng

et al. 2024

Orphanet J Rare Dis

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Background Trio-based whole-exome sequencing (trio-WES) enables identification of pathogenic variants, including copy-number variants (CNVs), in children with unexplained neurodevelopmental delay (NDD) and neurodevelopmental comorbidities (NDCs), including autism spectrum disorder (ASD), epilepsy, and attention deficit hyperactivity disorder. Further phenotypic and genetic analysis on trio-WES-tested NDD-NDCs cases may help to identify key phenotypic factors related to higher diagnostic yield of using trio-WES and novel risk genes associated with NDCs in clinical settings. Methods In this study, we retrospectively performed phenotypic analysis on 163 trio-WES-tested NDD-NDCs children to determine the phenotypic differences between genetically diagnosed and non-genetically diagnosed groups. Additionally, we conducted genetic analysis of ASD genes with the help of Simons Foundation for Autism Research Institute (SFARI) Gene database to identify novel possible ASD-risk genes underlying genetic NDD conditions. Results Among these 163 patients, pathogenic variants were identified in 82 cases (82/163, 50.3%), including 20 cases with CNVs. By comparing phenotypic variables between genetically diagnosed group (82 cases) and non-genetically diagnosed group (81 cases) with multivariate binary logistic regression analysis, we revealed that NDD-NDCs cases presenting with severe-profound NDD [53/82 vs 17/81, adjusted-OR (95%CI): 4.865 (2.213 – 10.694), adjusted-P < 0.001] or having multiple NDCs [26/82 vs 8/81, adjusted-OR (95%CI): 3.731 (1.399 – 9.950), adjusted-P = 0.009] or accompanying ASD [64/82 vs 35/81, adjusted-OR (95%CI): 3.256 (1.479 – 7.168), adjusted-P = 0.003] and head circumference abnormality [33/82 vs 11/81, adjusted-OR (95%CI): 2.788 (1.148 – 6.774), adjusted-P = 0.024] were more likely to have a genetic diagnosis using trio-WES. Moreover, 37 genes with monogenetic variants were identified in 48 patients genetically diagnosed with NDD-ASD, and 15 dosage-sensitive genes were identified in 16 individuals with NDD-ASD carrying CNVs. Most of those genes had been proven to be ASD-related genes. However, some of them (9 genes) were not proven sufficiently to correlate with ASD. By literature review and constructing protein-protein interaction networks among these 9 candidate ASD-risk genes and 102 established ASD genes obtained from the SFARI Gene database, we identified CUL4B, KCNH1, and PLA2G6 as novel possible ASD-risk genes underlying genetic NDD conditions. Conclusions Trio-WES testing is recommended for patients with unexplained NDD-NDCs that have severe-profound NDD or multiple NDCs, particularly those with accompanying ASD and head circumference abnormality, as these independent factors may increase the likelihood of genetic diagnosis using trio-WES. Moreover, NDD patients with pathogenic variants in CUL4B, KCNH1 and PLA2G6 should be aware of potential risks of developing ASD during their disease courses.

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Report of a patient with Temple–Baraitser syndrome

Cited by 9 publications

References 6 publications

Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3—a subgroup of K+ channelopathies

Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3—a subgroup of K+ channelopathies

Two cases of Temple–Baraitser syndrome

Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing

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