Wiedemann-Steiner syndrome ICD Q87.1

Wiedemann-Steiner syndrome is a very rare autosomal dominant malformation syndrome characterized by hypertrichosis cubiti associated with short stature, uniform facial features including long eyelashes, thick or arched eyebrows with lateral flare, a broad nasal bridge, and downward sloping and vertically narrowed palpebral fissures, mild to moderate intellectual disability, behavioral difficulties, and hypertrichosis of the elbows, arms, and back (Jones et al. 2012; Miyake et al. 2016). Furthermore: feeding difficulties, behavioral problems, and seizures.

Jones et al (2012) performed whole-exome sequencing in 4 patients with Wiedemann-Steiner syndrome and identified heterozygous de novo truncation mutations in the KMT2A gene in 3 of the 4 patients (159555.0001-159555.0003). Analysis of the KMT2A gene in 2 additional patients with a similar phenotype revealed 2 additional truncation mutations (159555.0004 and 159555.0005).

Miyake et al (2016) identified 6 different heterozygous mutations in the KMT2A gene in 6 unrelated children with WSS. In 4 patients, the mutations were shown to occur de novo (nonsense or frameshift mutations/missense mutations).

Treatment is focused on treating the symptoms.

Wiedemann et al (1989) reported a Caucasian boy with pre- and postnatal growth deficiency, psychomotor delay, round and flat face, short nose, hypertelorism, long philtrum, short palpebral fissures, low-set ears, and upturned palate. Other findings included an alternating convergent squint, widening of the renal calices, and short and thick limbs.

MacDermot et al. (1989) reported a mother and daughter with hairy elbows who also had short stature, rhizomelic shortening of the limbs, a round face, and a heavy jaw.

MacDermot et al. (1989) also reported a sporadic case in a 7-year-old boy with short stature and facial dysmorphism that included downward palpebral fissures, mild hypertelorism, and a short nose with thick nostrils.

Flannery et al (1989) described a 4.8-year-old girl with hairy elbows and short stature who also had facial asymmetry, developmental delay, and speech delay. She had hypertrichosis on the distal-lateral arms and proximal-lateral forearms, where the hair was longer, darker, and somewhat coarser than normal hair on the arms. Facial features included hypotonia and left-sided hypoplasia, left-sided ptosis, epicanthal folds, and a highly arched palate; she also had generalized hypotonia.

Edwards et al (1994) described a girl with hairy elbows, facial asymmetry, and delayed speech. She had right facial hypoplasia and right ptosis. There was circumcircular hypertrichosis affecting the right side of the lip and right zygomatic region, the lateral half of each arm between the deltoid base and the elbow, the right side of the trunk posteriorly, and the right posterior thigh.

Edwards et al (1994) noted similarities between this patient and the girl described by Flannery et al (1989) and suggested that it may be a distinct hypertrichosis syndrome associated with asymmetric facial growth and delayed development.

1. Beighton PH (1970) Familial hypertrichosis cubiti: hairy elbows syndrome. J Med Genet 7 158-160.
2. Edwards MJ et al (1994) Hypertrichosis 'cubiti' with facial asymmetry. Am J Med Genet 53: 56-58.
3. Flannery DB et al (1989) Hypertrichosis cubiti. Am J Med Genet 32: 482-483.
4. Jones WD et al (2012) De novo mutations in MLL cause Wiedemann-Steiner syndrome. Am J Hum Genet 91: 358-364.
5. Koc A et al (2007) A new case of hairy elbows syndrome (hypertrichosis cubiti). Genet. Counsel. 18: 325-330
6. Koenig, R., Meinecke, P., Kuechler, A., Schafer, D., Muller, D. Wiedemann-Steiner syndrome: three further cases. Am. J. Med. Genet. 152A: 2372-2375, 2010. [PubMed: 20803650, related citations] [Full Text].
7. Luo S et al (2021) Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann-Steiner syndrome. Mol Genet Genomic Med 9:e1798.
8. MacDermot, K. D., Patton, M. A., Williams, M. J. H., Winter, R. M. Hypertrichosis cubiti (hairy elbows) and short stature: a recognizable association. J. Med. Genet. 26: 382-385, 1989. [PubMed: 2738900, related citations] [Full Text].
9. Miyake N et al (2016) Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations. Clin Genet 89: 115-119.
10. Panagopoulos I et al (2021) Rare KMT2A-ELL and Novel ZNF56-KMT2A Fusion Genes in Pediatric T-cell Acute Lymphoblastic Leukemia. Cancer Genomics Proteomics 18:121-131.
11. Polizzi A et al (2005) Hypertrichosis cubiti (hairy elbow syndrome): a clue to a malformation syndrome. J Pediat Endocr Metab 18: 1019-1025.
12. Sorge G et al. (2002) The hairy elbows syndrome: report of a case with a particularly severe phenotype. Ital J Pediat 28: 322-325.
13. Wiedemann HR et al (1989) A syndrome of abnormal facies, short stature, and psychomotor retardation. :In: Atlas of Clinical Syndromes: A Visual Aid to Diagnosis for Clinicians and Practicing Physicians. (2nd ed.) London: Wolfe Publishing Ltd. (pub.):198-199.