Wiedemann–Steiner syndrome
| Wiedemann–Steiner syndrome | |
|---|---|
| Other names | Hypertrichosis-short stature-facial dysmorphism-developmental delay syndrome[1] |
Wiedemann–Steiner syndrome (WSS)[2] is a rare genetic disorder that causes developmental delay, unusual facial features, short stature, and reduction in muscle tone (hypotonia). The syndrome was originally described in 1989[3] by Hans-Rudolf Wiedemann. The genetic basis for the syndrome was identified by Dr. Wendy D. Jones in 2012.[4] The first case was reported in 1989 by Wiedemann and colleagues which reported a Caucasian boy with pre- and postnatal growth deficiency, psychomotor delay, and a round and flat face, short nose, widely spaced eyes, long philtrum, short palpebral fissures, low-set ears, and high-arched palate. Other findings included an alternating convergent squint, dilatation of the renal calyces, and short and thick limbs. Later decades brought about more finding and descriptions of this disorder.[5]
Signs and symptoms
[edit]Features described in Wiedemann–Steiner syndrome include:[6]
- Short stature
- Developmental delay
- Low muscle tone (hypotonia) especially in infancy
- Characteristic facial features
- Hairy elbows (hypertrichosis cubiti)
Cause
[edit]Wiedemann–Steiner syndrome results from mutations in the MLL (also known as KMT2A) gene on the long arm of chromosome 11.[4] The gene encodes a histone-modification enzyme — that is, it helps modify the expression of other genes.[5] The condition is autosomal dominant, meaning that only one abnormal copy of the gene is needed for a person to have the syndrome.
The mechanism by which mutations in the MLL gene cause the phenotype of Wiedemann–Steiner syndrome is not yet known.[5]
Screening
[edit]If Wiedemann–Steiner syndrome is suspected, analysis of the MLL gene can be carried out. Otherwise, it may be diagnosed by whole-exome sequencing or whole genome sequencing.
There have also been patients with Wiedemann–Steiner syndrome who were initially mis-diagnosed with Kabuki syndrome.[7]
Treatment
[edit]There is no specific cure or treatment for Wiedemann–Steiner syndrome. Children with this condition may benefit from a range of supportive treatments such as physiotherapy, speech therapy, supplementary nutrition for poor feeding, and special educational support.[6]
Epidemiology
[edit]A little over 1000 people have been documented with the condition worldwide. Once thought to have an incidence of 1 in 1,000,000, some research has suggested the incidence may be as high as 1 in 40,000 [5] The approximate number of WSS cases are seemingly low today but offspring of those with WSS have half the chance of having the disorder themselves.[2] There’s no current evidence of life expectancy of individuals with WSS is shortened.[7]
References
[edit]- ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Wiedemann Steiner syndrome". www.orpha.net. Retrieved 14 March 2019.
{{cite web}}: CS1 maint: numeric names: authors list (link) - ^ a b "What is Wiedemann–Steiner Syndrome? – WSS Foundation". WSS Foundation. Retrieved 2017-10-28.
- ^ Wiedemann H-R, Kunze J, Dibbern H. 1989. Atlas der klinischen Syndrome für Klinik und Praxis 3rd edition. Stuttgart: Schattauer. pp 198–199. ISBN 9783794516827
- ^ a b Jones, WD; Dafou, D; McEntagart, M; Woollard, WJ; Elmslie, FV; Holder-Espinasse, M; Irving, M; Saggar, AK; Smithson, S; Trembath, RC; Deshpande, C; Simpson, MA (10 August 2012). "De novo mutations in MLL cause Wiedemann–Steiner syndrome". American Journal of Human Genetics. 91 (2): 358–64. doi:10.1016/j.ajhg.2012.06.008. PMC 3415539. PMID 22795537.
- ^ a b c d Aggarwal, Anjali; Rodriguez-Buritica, David F.; Northrup, Hope (June 2017). "Wiedemann-Steiner syndrome: Novel pathogenic variant and review of literature". European Journal of Medical Genetics. 60 (6): 285–288. doi:10.1016/j.ejmg.2017.03.006. ISSN 1878-0849. PMID 28359930.
- ^ a b Steiner, CE; Marques, AP (April 2000). "Growth deficiency, mental retardation and unusual facies". Clinical Dysmorphology. 9 (2): 155–6. doi:10.1097/00019605-200009020-00021. PMID 10826636.
- ^ a b Miyake, N., Tsurusaki, Y., Koshimizu, E., Okamoto, N., Kosho, T., Brown, N.J., Tan, T.Y., Yap, P.J.J., Suzumura, H., Tanaka, T., Nagai, T., Nakashima, M., Saitsu, H., Niikawa, N. and Matsumoto, N. (January 2016). "Delineation of clinical features in Wiedemann–Steiner syndrome caused by KMT2A mutations". Clinical Genetics. 89 (1): 115–119. doi:10.1111/cge.12586. PMID 25810209. S2CID 205000688.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
7. (Replacement) Sheppard SE, Quintero-Rivera F. Wiedemann-Steiner Syndrome. 2022 May 26. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022.
8. Koenig, R., Meinecke, P., Kuechler, A., Schäfer, D., & Müller, D. (2010). Wiedemann-Steiner syndrome: Three further cases. American Journal of Medical Genetics Part A, 152A(9), 2372–2375. https://doi.org/10.1002/ajmg.a.33587