Wiedemann-steiner syndrome with a de novo mutation in KMT2A: A case report

Medicine (Baltimore). 2020 Apr;99(16):e19813. doi: 10.1097/MD.0000000000019813.

Abstract

Rationale: Wiedemann-Steiner syndrome (WDSTS, online mendelian inheritance in man 605130) is a rare autosomal dominant disorder characterized by hypertrichosis cubiti. Here, we report a Chinese boy who do not show the characteristic of hypertrichosis cubiti, and was misdiagnosed as blepharophimosis-ptosis-epicanthus inversus syndrome at first. We found a de novo frameshift mutation (p.Glu390Lysfs*10) in the KMT2A gene, which was not reported before. Our study increases the cohort of Chinese WDSTS patients, and expand the WDSTS phenotypic and variation spectrum.

Patient concerns: The patient demonstrated typical craniofacial features of blepharophimosis-ptosis-epicanthus inversus syndrome, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus, besides he had congenital heart disease (ventricular septal defects), strabismus, hypotonia, amblyopia, delayed speech and language development, delayed psychomotor development, and amblyopia (HP:0000646) which was not reported before.

Diagnosis: FOXL2 gene was cloned and sequenced, however, there was no mutation detected in this patient. The result of Chromosomal microarray analysis was normal. The patient was diagnosed as WDSTS by whole exome sequencing.

Interventions: The patient received cardiac surgery, frontalis suspension and regular speech and occupational therapy. He also treated with growth hormone (GH).

Outcomes: The patient's symptoms are improved after cardiac surgery and frontalis suspension, he can express himself well now and had a 10 cm gain in height.

Lessons: As the relationship between genotype and phenotype becomes more and more clear, WES is incredibly powerful tool to diagnose the disease of WDSTS.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / therapy
  • Asian People / genetics
  • Blepharophimosis / diagnosis*
  • Child
  • Contracture / diagnosis
  • Contracture / genetics*
  • Contracture / therapy
  • Diagnostic Errors
  • Exome Sequencing / methods
  • Facies
  • Genotype
  • Growth Disorders / diagnosis*
  • Growth Disorders / etiology
  • Growth Disorders / genetics*
  • Growth Disorders / therapy
  • Growth Hormone / therapeutic use
  • Heart Defects, Congenital / diagnosis*
  • Heart Defects, Congenital / surgery
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Hypertrichosis / congenital*
  • Hypertrichosis / diagnosis
  • Hypertrichosis / etiology
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Intellectual Disability / therapy
  • Male
  • Microcephaly / diagnosis
  • Microcephaly / genetics*
  • Microcephaly / therapy
  • Mutation
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Phenotype
  • Skin Abnormalities / diagnosis*
  • Treatment Outcome
  • Urogenital Abnormalities / diagnosis*

Substances

  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Growth Hormone
  • Histone-Lysine N-Methyltransferase

Supplementary concepts

  • Blepharophimosis, Ptosis, and Epicanthus Inversus
  • Growth Deficiency and Mental Retardation with Facial Dysmorphism
  • Hairy elbows