DESSH: Desanto-Shinawi Syndrome Corporation

Vernon,  NJ 
United States
https://www.dessh.org/
  • Booth: 230


 Press Releases

  • (Jul 18, 2019)

     DeSanto-Shinawi Syndrome

     

    June 3, 2019


    To Whom It May Concern:

     

    I write to you today as a parent of a child with a very rare and newly discovered genetic syndrome. DeSanto-Shinawi Syndrome (DESSH) impacts less than 100 people worldwide. It is the result of a mutation of the WAC gene and manifests itself through global developmental delays, hypotonia, speech difficulties, seizures, attention deficit, behavioral problems, autistic traits, intellectual disability, speech delays, and fine and gross motor deficiencies. When our son Leo was first diagnosed with DESSH we did not have a lot of information and did not know what to expect. Our doctors did not know much about DESSH and had never met a child with the syndrome. We knew were facing an uphill battle. 

     

    Since Leo’s diagnosis more than two years ago, my wife and I have taken it upon ourselves to learn more about DESSH with the hopes that a cure can be found for Leo, those like him, and for future children diagnosed with this syndrome. After we took a trip to St. Louis in November to meet Dr. Marwan Shinawi, the doctor that first discovered DESSH and after whom the syndrome is named, my wife and I experienced newfound hope for Leo’s future. Dr. Shinawi was able to share with us some exciting conclusions from studies that had recently been conducted which suggest that genetic syndromes like DESSH could be curable. In order to fully prove the case and its applicability to DESSH more specifically, however, it would require additional studies and a full-time researcher to conduct lab experiments on mice and flies. Through these experiments, Dr. Shinawi believes, a procedure to replace the mutated WAC gene could be formulated through mice and flies, which could later be performed as a cure for DESSH for humans. 

     

    The cost of a full-time researcher would approach approximately $100,000. Although discouraged by the cost, Dr. Shinawi filled my wife and me with a sense of purpose and drive when he said: “If you don’t advocate for a cure and work to fundraise for this research, literally no one else will.” It was a sobering truth, but this call to action is the reason I am writing to you today. I write with the hope that you might consider donating to our cause and helping to cure DESSH for my son and others like him. If you have the means or interest to contribute please visit our website: www.dessh.org and click on the “donate” tab. We operate as a non-profit organization and will soon be recognized with our 501c3 status. Thank you in advance for your consideration and please feel free to contact me with any other questions you might have about DESSH or ways you can help.

     

    Sincerely,

     

    Joseph S. Piccirillo

  • DESANTO-SHINAWI SYNDROME; DESSH

    Alternative titles; symbols

    DEVELOPMENTAL DELAY, BEHAVIORAL ABNORMALITIES, FACIAL DYSMORPHISM, AND OCULAR ABNORMALITIES

    Other entities represented in this entry:

    CHROMOSOME 10p12-p11 DELETION SYNDROME, INCLUDED

    Phenotype-Gene Relationships

    Location Phenotype Phenotype 
    MIM number
    Inheritance Phenotype 
    mapping key
    Gene/Locus Gene/Locus 
    MIM number
    10p12.1 Desanto-Shinawi syndrome 616708 AD 3 WAC 615049
    Clinical Synopsis
       
     

     TEXT

    A number sign (#) is used with this entry because of evidence that DeSanto-Shinawi syndrome (DESSH) is caused by heterozygous mutation in the WAC gene (615049) on chromosome 10p11.

    Some patients with an overlapping phenotype have a deletion at chromosome 10p12-p11 encompassing several genes and consistent with a contiguous gene deletion syndrome.

     Description

    DeSanto-Shinawi syndrome is a rare neurodevelopmental disorder characterized by global developmental delay apparent in infancy or early childhood and associated with characteristic dysmorphic facial features, such as broad forehead, depressed nasal bridge with bulbous nasal tip, and deep-set eyes. Most patients also have gastrointestinal and mild ocular abnormalities, as well as behavioral problems (summary by DeSanto et al., 2015). 

     Clinical Features

    DeSanto et al. (2015) reported 6 children, including 2 sibs, of various ethnic origins, with global developmental delay noted in the first year of life and dysmorphic features. The patients ranged from 15 months to 11 years in age at the time of the report. Two patients were non-verbal, and the others showed delayed language acquisition. Behavioral abnormalities were variable but common, and included aggression, anxiety, and attention deficit-hyperactivity disorder, and autistic features. All had hypotonia and gastrointestinal difficulties, mainly feeding difficulties and constipation. Dysmorphic features included broad, prominent forehead, flat nasal bridge with bulbous tip and flaring nostrils, hypertelorism, synophrys, and strabismus. More variable dysmorphic features included brachycephaly, deep-set eyes, posteriorly rotated and/or simple ears, thin upper lip, downturned mouth, inverted nipples. Three patients had myopia and astigmatism, and an unrelated patient had sensorineural hearing loss. 

     Cytogenetics

    Wentzel et al. (2011) reported 6 unrelated children with developmental delay and common dysmorphic features associated with a heterozygous de novo deletion of chromosome 10p12-p11. All of the deletions had different breakpoints and ranged in size from 1 to 10 Mb with a common overlap of 360 kb, including the WAC gene. Most patients also had speech delay and hyperactive, aggressive, and/or autistic behavior. Visual abnormalities, such as hyperopia, strabismus, astigmatism, and myopia, were common, as were variable cardiac malformations, such as patent ductus arteriosus, septal defects, pulmonary valvular stenosis, and coarctation of the aorta. Two patients had seizures. Common dysmorphic features included deep-set eyes, downslanting or short palpebral fissures, synophrys, low-set eyebrows, dysplastic ears, bulbous nasal tip, thin upper lip, full cheeks, and short neck. Wentzel et al. (2011) noted the phenotypic similarities to a patient reported by Shahdadpuri et al. (2008) who also had a de novo heterozygous 10-Mb deletion of chromosome 10p12.1-p11.21, containing over 50 genes. The patient reported by Shahdadpuri et al. (2008) also had pseudoarthrosis of the clavicle, thin corpus callosum, and a 'beaten copper' appearance of the cranium without craniosynostosis (see 118980). 

    Okamoto et al. (2012) reported 2 unrelated Japanese children with developmental delay and common maxillofacial abnormalities associated with a heterozygous deletion at chromosome 10p12-p11. The deletions overlapped for 957 kb and included 4 genes: ARMC4 (615408), MPP7 (610973), WAC, and BAMBI (604444). Both children had frontal bossing, midface retrusion, coarse face, downslanting palpebral fissures, synophrys, deep-set eyes, epicanthus, wide nasal bridge, wide mouth, absent Cupid bow, downturned corners of the mouth, and large tongue. One also had malformed auricles, congenital cardiac anomalies, and short fingers with camptodactyly. The other child had a bulbous nose, deafness, and short stature with growth hormone deficiency. Brain imaging in both children was normal. The deletion was confirmed to be de novo in 1 of the patients.

     Molecular Genetics

    In 6 children, including 2 sibs, with DeSanto-Shinawi syndrome, DeSanto et al. (2015) identified 5 different heterozygous truncating mutations in the WAC gene (615049.0002-615049.0006). The mutation in the sibs was postulated to have resulted from germline mosaicism in 1 of the parents; the remaining mutations occurred de novo. The mutations were found by whole-exome sequencing; functional studies were not performed, but all were predicted to result in a loss of function. 

    DeSanto et al. (2015) noted that Hamdan et al. (2014) had identified a de novo heterozygous truncating mutation in the WAC gene (615049.0001) in a woman with moderate intellectual disability. That patient was part of a cohort of 41 child-parent trios, in which the child had intellectual disability, who underwent exome sequencing. 

     REFERENCES

    1. DeSanto, C., D'Aco, K., Araujo, G. C., Shannon, N., DDD Study, Vernon, H., Rahrig, A., Monaghan, K. G., Niu, Z., Vitazka, P., Dodd, J., Tang, S., and 9 others. WAC loss-of-function mutations cause a recognizable syndrome characterised by dysmorphic features, developmental delay and hypotonia and recapitulate 10p11.23 microdeletion syndrome. J. Med. Genet. 52: 754-761, 2015. [PubMed: 26264232related citations] [Full Text]

    2. Hamdan, F. F., Srour, M., Capo-Chichi, J.-M., Daoud, H., Nassif, C., Patry, L., Massicotte, C., Ambalavanan, A., Spiegelman, D., Diallo, O., Henrion, E., Dionne-Laporte, A., Fougerat, A., Pshezhetsky, A. V., Venkateswaran, S., Rouleau, G. A., Michaud, J. L. De novo mutations in moderate or severe intellectual disability. PLoS Genet. 10: e1004772, 2014. Note: Electronic Article. [PubMed: 25356899imagesrelated citations] [Full Text]

    3. Okamoto, N., Hayashi, S., Masui, A., Kosaki, R., Oguri, I., Hasegawa, T., Imoto, I., Makita, Y., Hata, A., Moriyama, K., Inazawa, J. Deletion at chromosome 10p11.23-p12.1 defines characteristic phenotypes with marked midface retrusion. J. Hum. Genet. 57: 191-196, 2012. [PubMed: 22258158related citations] [Full Text]

    4. Shahdadpuri, R., de Vries, B., Pfundt, R., de Leeuw, N., Reardon, W. Pseudoarthrosis of the clavicle and copper beaten skull associated with chromosome 10p11.21p12.1 microdeletion.Am. J. Med. Genet. 146A: 233-237, 2008. [PubMed: 18080323related citations] [Full Text]

    5. Wentzel, C., Rajcan-Separovic, E., Ruivenkamp, C. A. L., Chantot-Bastaraud, S., Metay, C., Andrieux, J. Anneren, G., Gijsbers, A. C. J., Druart, L., Hyon, C., Portnoi, M.-F., Stattin, E.-L., Vincent-Delorme, C., Kant, S. G., Steinraths, M., Marlin, S., Giurea, I., Thuresson, A.-C.Genomic and clinical characteristics of six patients with partially overlapping interstitial deletions at 10p12p11. Europ. J. Hum. Genet. 19: 959-964, 2011. [PubMed: 21522184imagesrelated citations] [Full Text]

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