title: Dysmorphic features, cognitive disability, chronic inflammation, and predisposition to vascular disease in two sisters:  a new autosomal recessive disorder?
abstract: A 20-year-old woman presented with mental retardation and a history of stroke related to moyamoya disease at the age of 8 years. She had cognitive impairment which became more pronounced after the stroke. This patient's parents were first cousins and six close family relatives had strokes in their 60s or 70s. The patient's 16-year-old sister had learning disability, chronic muscle pain, and an ECG suggestive of previous hypoxemic heart injury. The two sisters had similar dysmorphic facial appearance including a prominent philtrum, bulbous nose, and severe acne. They both had increased subcutaneous tissue in their faces, whereas their bodies were slim. Both sisters were found to have elevated levels of rheumatoid factor, C-reactive protein, and erythrocyte sedimentation rate on repeat measurements. Partial autoimmunity screening in one of the patients was negative. Chromosome analysis and array comparative genomic hybridization analyses were also normal. Nerve conduction findings in the younger sister were consistent with distal, predominantly motor, demyelinating neuropathy localized to the lower extremities. We propose that these two sisters suffer from a new autosomal recessive syndrome. Carrier status for this condition may predispose to later onset stroke.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island Maimonides Medical Center, Brooklyn Columbia Presbyterian Hospital Center New York University, New York, New York, USA.
authors.forename: Milen
authors.initials: M
authors.lastname: Velinov
authors.forename: Natalia
authors.initials: N
authors.lastname: Dolzhanskaya
authors.forename: Prema
authors.initials: P
authors.lastname: Ramaswamy
authors.forename: Laura
authors.initials: L
authors.lastname: Barinstein
authors.forename: R Morgan
authors.initials: RM
authors.lastname: Stuart
authors.forename: Philip
authors.initials: P
authors.lastname: Kahn
authors.forename: Neil
authors.initials: N
authors.lastname: Feldstein
authors.forename: Ricardo E
authors.initials: RE
authors.lastname: Madrid
mesh_terms: D000293:Adolescent; D057215:Body Dysmorphic Disorders / Q000235:genetics; D060825:Cognitive Dysfunction / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics; D009072:Moyamoya Disease / Q000235:genetics*; D035781:Siblings; D020521:Stroke / Q000235:genetics; D014652:Vascular Diseases / Q000235:genetics; D055815:Young Adult