Elsahy–Waters syndrome: Evidence for autosomal recessive inheritance

Castori, Marco; Cascone, Piero; Valiante, Michele; Laino, Luigi; Iannetti, Giorgio; Hennekam, Raoul C. M.; Grammatico, Paola

doi:10.1002/ajmg.a.33634

Cited by 13 publications

(16 citation statements)

References 10 publications

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“…Abnormal dentin formation with variable features is also observed in the following syndromes; Ehlers‐Danlos syndrome type I (De Coster et al ) and type VIIc (De Coster et al ), spondylometaphyseal dysplasia associated with joint laxity and dentinogenesis imperfecta (Goldblatt et al ; Bonaventure et al ; Unger et al ), Elashy‐Waters Brachio‐skeleto‐genital syndrome (Castori et al ), immuno‐osseous dysplasia, Schimke type (da Fonseca ), and odontodysplasia (Regional odontodysplasia, not listed in Table 2, Kantaputra et al ).…”

Section: Congenital Anomalies In Dentin (Table )mentioning

confidence: 99%

Odontoblasts: Specialized hard‐tissue‐forming cells in the dentin‐pulp complex

Kawashima

Okiji

2016

Congenital Anomalies

134

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Odontoblasts are specialized cells that produce dentin and exhibit unique morphological characteristics; i.e., they extend cytoplasmic processes into dentinal tubules. While osteoblasts, which are typical hard-tissue-forming cells, are generated from mesenchymal stem cells during normal and pathological bone metabolism, the induction of odontoblasts only occurs once during tooth development, and odontoblasts survive throughout the lives of healthy teeth. During the differentiation of odontoblasts, signaling molecules from the inner enamel epithelium are considered necessary for the differentiation of odontoblast precursors, i.e., peripheral dental papilla cells. If odontoblasts are destroyed by severe external stimuli, such as deep caries, the differentiation of dental pulp stem cells into odontoblast-like cells is induced. Various bioactive molecules, such as non-collagenous proteins, might be involved in this process, although the precise mechanisms responsible for odontoblast differentiation have not been fully elucidated. Recently, our knowledge about the other functional activities of odontoblasts (apart from dentin formation) has increased. For example, it has been suggested that odontoblasts might act as nociceptive receptors, and surveillance cells that detect the invasion of exogenous pathogens. The regeneration of the dentin-pulp complex has recently gained much attention as a promising future treatment modality that could increase the longevity of pulpless teeth. Finally, congenital dentin anomalies, which are concerned with the disturbance of odontoblast functions, are summarized.

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Section: Congenital Anomalies In Dentin (Table )mentioning

confidence: 99%

Odontoblasts: Specialized hard‐tissue‐forming cells in the dentin‐pulp complex

Kawashima

Okiji

2016

Congenital Anomalies

134

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“…All patients show developmental delay, particularly in the cognitive domain, and (borderline) ID is apparent at older age (Table ). Other manifestations include dental and skeletal anomalies (Table ) (Castori et al, ; Taskiran et al, ). Of note, six of seven males had hypospadias (Table ).…”

Section: Discussionmentioning

confidence: 99%

“…This has also raised concerns that EWS may not be a distinct disorder but rather a variable presentation of X‐linked Opitz‐G/BBB syndrome (MIM 300000) (Hennekam, Krantz, & Allanson, ). However, the brother and sister reported by Castori et al () strongly argued for an autosomal recessive inheritance. In addition, several clinical features of EWS appear to distinguish it from Opitz‐G/BBB, including proptosis, thick eyebrows, and skeletal abnormalities.…”

Section: Introductionmentioning

confidence: 96%

“…Additional features included hypogenitalism, pectus excavatum, and C‐spine fusion, hence the name branchial‐skeletal‐genital syndrome was introduced (MIM 211380) (el‐Sahy & Waters, ). The extreme rarity of the syndrome is evidenced by the near lack of follow‐up case reports apart from detailed description of the original cases by Witkop () and Wedgwood, Curran, Lavelle, and Trott, (), as well as two affected siblings each by Castori et al () and Taskiran et al () (Wedgwood et al, ; Witkop, ). Although suggested to represent a novel entity, the two brothers described by Balci, Kayikcioglu, and Dagli, () probably had Elsahy‐Waters Syndrome (EWS).…”

Section: Introductionmentioning

confidence: 99%

“…Until the report by Castori et al (), the mode of inheritance of EWS has been debated given the strictly male and sporadic nature of the reported cases. This has also raised concerns that EWS may not be a distinct disorder but rather a variable presentation of X‐linked Opitz‐G/BBB syndrome (MIM 300000) (Hennekam, Krantz, & Allanson, ).…”

Section: Introductionmentioning

confidence: 99%

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Elsahy–Waters syndrome is caused by biallelic mutations in CDH11

Harms

Nampoothiri

Anazi

et al. 2017

American J of Med Genetics Pt A

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Elsahy-Waters syndrome (EWS), also known as branchial-skeletal-genital syndrome, is a distinct dysmorphology syndrome characterized by facial asymmetry, broad forehead, marked hypertelorism with proptosis, short and broad nose, midface hypoplasia, intellectual disability, and hypospadias. We have recently published a homozygous potential loss of function variant in CDH11 in a boy with a striking resemblance to EWS. More recently, another homozygous truncating variant in CDH11 was reported in two siblings with suspected EWS. Here, we describe in detail the clinical phenotype of the original CDH11-related patient with EWS as well as a previously unreported EWS-affected girl who was also found to have a novel homozygous truncating variant in CDH11, which confirms that EWS is caused by biallelic CDH11 loss of function mutations. Clinical features in the four CDH11 mutation-positive individuals confirm the established core phenotype of EWS. Additionally, we identify upper eyelid coloboma as a new, though infrequent clinical feature. The pathomechanism underlying EWS remains unclear, although the limited phenotypic data on the Cdh11 mouse suggest that this is a potentially helpful model to explore the craniofacial and brain development in EWS-affected individuals.

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Homozygous indel mutation in CDH11 as the probable cause of Elsahy–Waters syndrome

Taşkıran

Karaosmanoğlu

Koşukçu

et al. 2017

American J of Med Genetics Pt A

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Two sisters from a consanguineous couple were seen in genetics department for facial dysmorphic features and glaucoma. They both had broad foreheads, hypertelorism, megalocorneas, thick eyebrows with synophrys, flat malar regions, broad and bulbous noses, and mild prognathism. Both had glaucoma, younger one also had cataracts and phthisis bulbi. Other findings included bilateral partial cutaneous syndactyly of 2nd and 3rd fingers, history of impacted teeth with dentigerous cyst in the elder one, and intellectual disability (mild and borderline). The sisters were considered to have Elsahy-Waters syndrome. In order to elucidate the underlying molecular cause, sisters and their healthy parents were genotyped by SNP arrays, followed by homozygosity mapping. Homozygous regions were further analyzed by exome sequencing in one affected individual. A homozygous indel variant segregating with the condition was detected in CDH11 (c.1116_1117delinsGATCATCAG, p.(Ile372MetfsTer9)), which was then validated by using Sanger sequencing. CDH11 encodes cadherin 11 (osteo-cadherin) that regulates cell-cell adhesion, cell polarization and migration, as well as osteogenic differentiation. Further experiments revealed that CDH11 expression was decreased in patient-derived fibroblasts as compared to the heterozygous parent and another healthy donor. Immunostaining showed absence of the protein expression in patient fibroblasts. In addition, cell proliferation rate was slow and osteogenic differentiation potential was delayed. We consider that this study reveals loss-of-function mutations in CDH11 as a probable cause of this phenotype. Next generation sequencing in further patients would both prove this gene as causative, and finely delineate this clinical spectrum further contributing in identification of other possibly involved gene(s).

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Elsahy–Waters syndrome: Evidence for autosomal recessive inheritance

Cited by 13 publications

References 10 publications

Odontoblasts: Specialized hard‐tissue‐forming cells in the dentin‐pulp complex

Odontoblasts: Specialized hard‐tissue‐forming cells in the dentin‐pulp complex

Elsahy–Waters syndrome is caused by biallelic mutations in CDH11

Homozygous indel mutation in CDH11 as the probable cause of Elsahy–Waters syndrome

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