Warsaw Syndrome

Ebba Alkhunaizi; Robert M Brosh Jr; Fowzan S Alkuraya; David Chitayat

Warsaw Syndrome

Review

In: GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.

2019 Jun 6.

Authors

Ebba Alkhunaizi¹, Robert M Brosh Jr², Fowzan S Alkuraya³, David Chitayat¹

Book Editors

Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Lora JH Bean, Karen W Gripp, Anne Amemiya

Affiliations

¹ The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital;, Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
² Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
³ Department of Genetics, King Faisal Specialist Hospital and Research Center;, Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

PMID: 31169992
Bookshelf ID: NBK541972

Excerpt

Clinical characteristics: Warsaw syndrome is characterized by the clinical triad of severe congenital microcephaly, growth restriction, and sensorineural hearing loss due to cochlear hypoplasia. Intellectual disability is typically in the mild-to-moderate range. Severe speech delay is common. Gross and fine motor milestones are usually attained at the usual time, although a few individuals have mild delays. Additional common features include skeletal anomalies and cardiovascular anomalies. Abnormal skin pigmentation and genitourinary malformations have also been reported. Some individuals have had increased chromosome breakage and radial forms on cytogenetic testing of lymphocytes treated with diepoxybutane and mitomycin C.

Diagnosis/testing: The diagnosis of Warsaw syndrome is established in a proband by identification of biallelic pathogenic variants in DDX11 on molecular genetic testing.

Management: Treatment of manifestations: Supplementary formula and/or gastrostomy tube as needed to optimize nutrition. Treatments for hearing loss include hearing aids, cochlear implantation, auditory brain stem implant; establishing system of communication and hearing habilitation that may include sign language, auditory therapy, speech therapy; educational programs designed for individuals with hearing impairment. Treatment of cardiac anomalies per cardiologist; treatment of genitourinary anomalies per nephrologist and/or urologist; early intervention and psychological evaluations; physical, occupational, and speech therapies.

Surveillance: Monitor growth, speech development, and educational needs with each visit; there is no consensus regarding tumor screening.

Genetic counseling: Warsaw syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the DDX11 pathogenic variants in the family are known.

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