25. Holmstrom G, Thomassen P, Broberger U. Maternal risk factors for ret- Download full-text
26. Shah VA, Yeo CL, Ling YL, Ho LY. Incidence, risk factors of retinopathy
of prematurity among very low birth weight infants in Singapore. Ann
Acad Med Singapore 2005;34:169-78.
Study Group. Eur J Pediatr 1997;156:939-43.
29. Xiong X, Demianczuk NN, Saunders LD, Wang FL, Fraser WD. Impact
of preeclampsia and gestational hypertension on birth weight by gesta-
tional age. Am J Epidemiol 2002;155:203-9.
30. Smith LE. Pathogenesis of retinopathy of prematurity. Semin Neonatol
31. Hellstrom A, Perruzzi C, Ju M, Engstrom E, Hard AL, Liu JL, et al. Low
IGF-I suppresses VEGF-survival signaling in retinal endothelial cells:
direct correlation with clinical retinopathy of prematurity. Proc Natl
Acad Sci U S A 2001;98:5804-8.
32. Hellstrom A, Carlsson B, Niklasson A, Segnestam K, Boguszewski M,
de LL, et al. IGF-I is critical for normal vascularization of the human ret-
ina. J Clin Endocrinol Metab 2002;87:3413-6.
33. Hellstrom A, Engstrom E, Hard AL, bertsson-Wikland K, Carlsson B,
is associatedwith retinopathy ofprematurityandother complicationsof
premature birth. Pediatrics 2003;112:1016-20.
34. Ferrazzi E, Bellotti M, Galan H, Pennati G, Bozzo M, Rigano S, et al.
Doppler investigation in intrauterine growth restriction–from qualita-
tive indices to flow measurements: a review of the experience of a collab-
orative group. Ann N Y Acad Sci 2001;943:316-25.
35. Soares CR, Silveira RC, Procianoy RS. Ophthalmic artery blood flow in
very-low-birth-weight preterm infants. Invest Ophthalmol Vis Sci 2010;
50 Years Ago in THE JOURNAL OF PEDIATRICS
Turner’s Syndrome in the Male
Steiker DD, Mellman MJ, Bongionvanni AM, Eberlein WR, Leboeuf G. J Pediatr 1961;58:321-9
drome (TS) were ‘‘chromatin negative’’ emerged only 7 years before this report. Using the ‘‘nuclear sexing’’ sys-
tem, the interpretation of the absence of Barr bodies (sex chromatin), based on the 1947 Jost experiments in rabbits,
was that individuals with TS were genetic males who had undergone prenatal castration resulting in female genitalia
with an abnormal genotype rather than a ‘‘chromosomal male’’ or case of ‘‘sex reversal’’ appeared only 2 years before
Steiker et al reported their five cases of apparent TS in males. Thus, it is easy to understand their confusion regarding
the relationship between these boys and the classic triad of sexual infantilism, congenital webbed neck, and cubitus
valgus that comprisedthe initial description of girls with TS. Not only is a female phenotypenow part of its definition,
but the manifestations of TS are believed to be primarily caused by haploinsufficiency of one or more of the multitude
of genes on the X chromosome, such as SHOX.
A likely candidate forwhat was presumed male Turnersyndrome is Noonan syndrome,which is caused by PTPN11
deletions in ?50% of cases. Although one or more of the five boys probably had Noonan syndrome, it is unlikely that
they all did, given the disparate phenotypes. Distinguishing among children with overlapping features such as short
stature, abnormal auricles, high arched palate, low posterior hairline, and short or webbed neck was surely a challenge
50 years ago, and, despite advances in molecular and clinical genetics, sometimes remains one to this day. The authors
are to be commended for attempting to reconcile a bewildering set of observations, causing them to go so far as to
suggest that the features of TS were unrelated to the emblematic chromosomal pattern. This insinuation might
seem preposterous to us today, but we should remember the importance of an open mind and consider every conceiv-
able explanation for our findings until the inexorable process of scientific discovery allows the ‘‘truth’’ to become
lthough described clinically more than two decades earlier, the recognition that most patients with Turner syn-
Erica A. Eugster, MD
Alan D. Rogol, MD, PhD
Riley Hospital for Children
THE JOURNAL OF PEDIATRICS
Vol. 158, No. 3
Fortes Filho et al