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]
| Wiedemann–Steiner syndrome | |
|---|---|
| Other names | Hypertrichosis-short stature-facial dysmorphism-developmental delay syndrome[1] |
Signs and symptoms
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
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
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
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
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
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