Phenotype and natural history in Marshall-Smith syndrome.
Marshall-Smith syndrome (MSS) is a distinctive entity of unknown etiology with fewer than 50 patients described in the medical literature to date. Through an International collaboration and use of an online wiki to facilitate data collection and sharing, we further delineate the phenotype and natural history of this syndrome. We present 15 new patients, the oldest being 30 years, provide an update on four previously published cases, and compare all patients with other patients reported in literature. Main clinical features are moderate to severe developmental delay with absent or limited speech, unusual behavior, dysharmonic bone maturation, respiratory compromise secondary to upper airway obstruction, short stature, and kyphoscoliosis. Facial features are characteristic with high forehead, underdeveloped midface, proptosis, anteverted nares, and everted lips. Minor abnormalities of brain morphology such as hypoplasia of the corpus callosum are common. Mortality from respiratory complications is high, but airway support increasingly allows survival into adulthood. Array-CGH was performed on 12 of the cohort and no copy number variants of clear clinical relevance were identified. The present study is the first reported use of an online wiki to aid delineation of a genetic syndrome, and illustrates its value in collecting detailed data in rare conditions.
Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, UK. a.shaw@ich.ucl.ac.uk
Adam C
AC
Shaw
Inge D C
ID
van Balkom
Mislen
M
Bauer
Trevor R P
TR
Cole
Marie-Ange
MA
Delrue
Arie
A
Van Haeringen
Eva
E
Holmberg
Samantha J L
SJ
Knight
Geert
G
Mortier
Sheela
S
Nampoothiri
Silvija
S
Pušeljić
Martin
M
Zenker
Valerie
V
Cormier-Daire
Raoul C M
RC
Hennekam
D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D001848:Bone Diseases, Developmental / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D025962:Septo-Optic Dysplasia / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D055815:Young Adult