Global developmental delay, osteopenia and ectodermal defect: a new syndrome.
Global developmental delay is a serious social problem. It is often unrecognized and the phenotypes are inadequately studied. To investigate the phenotypes of children with aspecific central nervous system (CNS) impairment (poor speech, maladaptive behavioral symptoms such as temper tantrums, aggressiveness, poor concentration and attention, impulsiveness, and mental retardation).


METHODS
Tertiary care hospital.


METHODS
Three children (two male siblings, and one unrelated girl).


METHODS
We used the results from clinical neurological evaluations; imaging and electrodiagnostic studies; metabolic and genetic tests; skin biopsies and bone mineral densitometry. All three children suffered from (A) global developmental delay, (B) osteopenia, and (C) identical skin defects. The skin ultrastructural abnormalities were abnormal keratin differentiation, consisting of hyperkeratosis and granular layer thickening; sweat gland abnormalities, consisting of focal, cytoplasmic clear changes in eccrine secretory cells; and melanocyte abnormalities, with both morphological changes (reduced number and size without evident dendritic processes), and functional changes (defects in the migration of melanosomes in the keratinocytes). These patients present a previously unrecognized syndrome. We retain useful to report this new association, to be recognized, in the next future, as a specific key-sign of a well-defined genetic defect.
Zannolli
Raffaella
R
Department of Paediatrics, Obstetrics and Reproductive Medicine, Section of Paediatrics, Policlinico Le Scotte, University of Siena, Siena, Italy. zannolli@unisi.it
Buoni
Sabrina
S
Macucci
Francesca
F
Santi
Maria M de
MM
Miracco
Flavia
F
Pierluigi
Mauro
M
Mogni
Massimo
M
Piomboni
Paola
P
Massafra
Maria R
MR
Galluzzi
Paolo
P
Livi
Walter
W
Cuccia
Aldo
A
Margollicci
Maria A
MA
Pucci
Lucia
L
Sacco
Palmino
P
Molinelli
Massimo
M
Burlina
Alberto B
AB
Swift
James A
JA
Fimiani
Michele
M
Zappella
Michele
M
Miracco
Clelia
C
D001706:Biopsy; D001851:Bone Diseases, Metabolic / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics*; D004475:Ectoderm / Q000473:pathology*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007633:Keratins / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000473:pathology; D035781:Siblings; D012867:Skin / Q000473:pathology*; D013545:Sweat Glands / Q000002:abnormalities; D013577:Syndrome
D007633:Keratins