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Williams–Beuren Syndrome
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Hui Zhang, Barbara Pober, Cheryl Klaiman, Robert Schultz
The reported incidence of WBS is between 1/10,000 and 20,000 (4,5), but this number may increase now that an accurate diagnostic tool is available. Although relatively rare, WBS has become increasingly well known in both professional and lay circles for its distinctive cognitive, personality, and behavior profiles. Williams–Beuren syndrome may present during infancy with characteristic physical features, cardiovascular problems, hypercalcemia, and/or failure to thrive. Diagnosis of WBS in older children is most often made during a workup for developmental delay. Recognition of WBS in adults frequently results from caregiver-referral following increased public awareness of this condition.
Epidemiology, Pathophysiology, Diagnosis and Treatment
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Susannah Clark, Patricia L. Roberts, Rocco Ricciardi
Some rare genetic diseases that show a predilection for the formation of diverticula also underscore the relationship between genetics and diverticular disease.28 Patients with the Williams–Beuren syndrome, caused by a deletion in a gene on chromosome-7 that codes for elastin, creating loss of function, have a three- to four-fold increased risk of diverticular disease compared to the general population. The age of diverticulitis onset is much younger in this population as well and has been seen in patients as young as 15 years of age. Type IV Ehlers–Danlos syndrome is another genetic disease affecting connective tissue due to heterozygous mutations in the procollagen-3A gene COL3A1. This mutation causes loss of smooth muscle and resultant formation of diverticula due to reduced strength of the submucosal tissue in the colon wall. The first presentation of Ehlers–Danlos is often a spontaneous bowel perforation that is sometimes misdiagnosed as complicated diverticulitis, given the commonality of diverticula in this population.
Lacrimal drainage system anomalies in Williams-Beuren syndrome
Published in Orbit, 2021
The article confirms to the Tenets of Declaration of Helsinki. Parent consent to publish was obtained. The facial images were in addition cropped in a way to depict only what is needed and protect the privacy of the patient. Williams-Beuren (WB) syndrome or simply Williams syndrome is a rare genetic disorder affecting 1:10000 to 1:20000 live-births.1,2 The disorder is secondary to contiguous gene deletion in a specific region of chromosome 7, called as the Williams-Beuren syndrome chromosome region (7q11.23).1–5 The deletion is sporadic in all cases. Clinical features along with genetic analysis using fluorescent in-situ hybridization (FISH) techniques are essential for the diagnosis.1–5 The WB syndrome affects numerous systems including connective tissue, cardiovascular, nervous, endocrine, genitourinary and musculoskeletal systems. Common systemic manifestations include dysmorphic facies, intellectual disabilities, typical cognitive profile, supravalvular aortic stenoses, intracardiac lesions, glucose intolerance, gastroesophageal reflux.1–5 Common ophthalmic manifestations include refractive errors, strabismus, reduced stereopsis, stellate iris and tortuous retinal vessels.3–9 Lacrimal drainage anomalies are rarely described with no further details of those reported patients.3–5 The present case describes multiple lacrimal drainage anomalies in a child with Williams-Beuren syndrome.
The Prenatal Diagnosis of Seven Fetuses with 7q11.23 Microdeletion or Microduplication
Published in Fetal and Pediatric Pathology, 2020
Yinghui Dang, Shanning Wan, Yunyun Zheng, Tingting Song, Chunyan Li, Yu Li, Jianfang Zhang
Copy number variants (CNVs) of the Williams–Beuren syndrome (WBS; OMIM: 194050) 7q11.23 region are the cause of neurodevelopmental disorders with multi-system involvement and variable expressivity. The WBS was named 7q11.23 microdeletion syndrome, which frequency is 1/7500–1/10,000 live births [1]. In turn, the phenotype of patients carrying 7q11.23 microduplications, named 7q11.23 microduplication syndrome (OMIM: 609757), includes prominent speech delay and less distinctive facial dysmorphisms [2]. The common microdeletion/microduplication ranges in size from 1.5 to 1.8 Mb and spans approximately 26–28 genes [3]. Most of the currently known WBS cases are due to spontaneous chromosomal changes in their parents’ germ cells (i.e., sperm and eggs). Only a small percentage of patients genetically inherit their parents' chromosomal alterations [4].
Exome sequencing identification of susceptibility genes in Chinese patients with keratoconus
Published in Ophthalmic Genetics, 2020
Liyan Xu, Kaili Yang, Qi Fan, Yuwei Gu, Bo Zhang, Chenjiu Pang, Shengwei Ren
Among all the susceptibility genes, TRANK1 is found on chromosome 3 and encodes tetratricopeptide repeat and ankyrin repeat containing 1. The protein presents significant expression in brain and has been associated with DNA/ATP binding or DNA repair (27). Previous study indicated the decreased expression of TRANK1 perturbed expression of many genes involved in neural development and differentiation (28). Thus, the variant (c.1168 T > C) in THANK1 might affect KC via influencing ocular development. ERMP1, located on 9p24, is a zinc-binding protease belonging to the peptidase M28 family, with nine predicted transmembrane domains normally localized in endoplasmic reticulum (29). Grandi et al. (29) found ERMP1 might play roles in the defense against oxidative stress. Studies have identified oxidative stress is implicated in the pathogenesis of KC (30,31). Then, we inferred the c.341A>T in ERMP1 might correlate with the disease. SDK2, located on 17q25, encodes a protein belong to immunoglobulin superfamily. It has been shown that SDK2 can promote lamina-specific connectivity in the development of retina (32). And it is important for the formation of the retinal circuit that detects differential motions (33). However, association studies between SDK2 and KC haven’t been reported. The relationship between SDK2 and KC still need to be further explored. There were also two collagen related genes, COL6A1 in chromosome 21 and COL9A3 in chromosome 20, identified as susceptibility genes for KC. COL6A1 encodes a constituent chain of type VI collagen, which is present in human corneal stroma (34). A recent genome wide association study found COL6A1 was associated with corneal biomechanical properties in KC, indicating a suggestive association with the disease (35). Similarly, COL9A3 encodes one of the three alpha chains of type IX collagen, which is also present in human cornea (36). But there existed no studies suggesting an associated between COL9A3 and ocular diseases to date. CNBD1 is cyclic nucleotide binding domain containing 1. And the CNBD1 had previously been implicated in the subcellular targeting of EPAC2A (catalytic domains of the cAMP sensors), playing important roles in cAMP signaling (37). In the present study, we found a stop gain mutation in CNBD1 might be relevant to KC. The dysfunction of CNBD1 might result in abnormal cAMP signaling, subsequently influencing the occurrence of the disease. KRT82 is a member of the keratin gene family. Variant in KRT82 has been identified as hotspot mutation in sporadic microsatellite-instable colorectal cancers (38). Studies have identified a correlation between other keratin gene and KC (39,40), but there existed no reports indicating a relationship of KRT82 with ocular diseases. NSUN5 is a cytosine-5 RNA methyltransferase which was selectively expressed in radial glial cells during embryonic cortex (41). The deletion of NSUN5 has been reported in about 95% patients with Williams–Beuren syndrome (41). And there have been reported several cases indicating an association between KC and Williams–Beuren syndrome (42–44). Therefore, we speculated there might be a potential role for NSUN5 in the pathogenesis of KC.