American Journal of Medical Genetics 131A:318 –319 (2004)

Research Letter
Congenital Mydriasis, Patent Ductus Arteriosus, and
Congenital Cystic Lung Disease: New Syndromic Spectrum?

To the Editor: cycloplentalate) did not alter the size of the pupils, the re-
fractive error was found to be less myopic, suggesting the
Congenital mydriasis is an extremely rare ophthalmic presence of some accommodative ability in each eye. Her near
condition involving aplasia of the iris sphincter muscles and point of accommodation was later measured at age 5 years as
hypofunction or hypoplasia of the dilator muscles resulting in reduced to 6 inches in each eye. Without reading glasses she
fixed dilated pupils, often bilateral [White and Fulton, 1937; could read only the equivalent of 20/80 in each eye. This was
Caccamise and Townes, 1976; Richardson and Schulenburg, improved to 20/20 with a reading addition of þ3.00 S in her
1992; Buys et al., 1993; Graf and Jungherr, 2002]. Some cases bifocals which she found useful. The pupils were round and
are associated with developmental delay and White’s cases in symmetrical, measuring 7 mm in the horizontal plane and
monozygotic female twins suggest inheritance to be either showed no movement, either constriction to light or dilation in
autosomal dominant or X-linked dominant with limited viabi- the dark, on clinical examination. There was absence of the iris
lity in males. Buys et al. [1993] initially reported an association collarette, the pupillary marginal pigmentary ruff, and the
between congenital mydriasis and patent ductus arteriosus in area of thickening characteristic of the pupillary sphincter.
a boy and Graf and Jungherr [2002] later described the defect The iris stroma surrounding the pupillary opening was
in two patients, suggesting a causal relationship in the patho- without radial or concentric iris folds and without stromal
genesis of the two defects. We describe another patient with crypts usually seen, i.e., the iris appeared flat. On the iris sur-
congenital mydriasis and patent ductus arteriosus, but with face were diffusely scattered small pigment clusters. There
additional findings of coarctation of the aorta, congenital cystic were remnant strands of the pupillary membrane in some
lung disease and other abnormalities. areas of the pupil and strands of pigment on the lens surface.
The proband is a 4-year-old girl followed by clinical genetics These iris and pupillary changes were symmetrical in both
since birth. Pregnancy history was unremarkable. She was eyes. Retinal exam was normal, without any unusual retinal
born at 38 weeks gestation, following spontaneous rupture of vessel tortuosity in either eye. Her ocular exam remained
membranes, with Apgars of 8 and 9 at 1 and 5 min respectively. unchanged when she was last seen at age 5 years.
She presented to the hospital at 2 months, due to a cough that Motor development was initially somewhat delayed, as the
developed into respiratory collapse. At that time, the patient proband first walked at 17 months. Currently, her develop-
was found to have a patent ductus arteriosus and coarctation of ment is age appropriate, apart from delayed expressive
the aorta. Surgery was performed to correct the heart defects, language for which she is receiving speech therapy.
but the lung disease persisted. Lung biopsy showed emphyse- Past investigations for the proband include an immunology
matous changes, consistent with a congenital cystic lung work-up, sweat test for cystic fibrosis, alpha-1-antitrypsin
disease. The patient has had recurrent respiratory infections analysis, a karyotype and FISH for microdeletion 22q11. The
since that time. Subsequent investigation for gastroesopha- results of all were either normal or negative. Due to the spon-
geal reflux showed nonrotation of the bowel (duodenum is taneous rupture of the membranes at 38 weeks, dilation of the
completely straight, small bowel is on the left side of the left ureter, mild joint laxity and soft skin, a skin biopsy has
abdomen, large bowel is on the right). This finding is thought to been arranged to investigate the possibility of a collagen tissue
be asymptomatic and probably unrelated to the gastroesopha- disorder from skin fibrobalsts. No abnormality was detected in
geal reflux. Recurrent urinary tract infections were investi- type I and type III procollagen and collagen.
gated, and renal ultrasound showed dilated calyces in the left Physical exam at 4 years and 7 months of age showed an alert
kidney, and dilation of the left ureter. The girl’s mother and active young girl. Her head circumference was below the
reported that her dentist noted that both of the proband’s 3rd centile at 47.5 cm. Her height was at the 10th centile at
lateral incisors have failed to develop. 98 cm, and weight was between the 10th and 25th centile at
The mother had noted both pupils to be constantly dilated 15.4 kg. She was noted to have mild joint laxity and soft skin.
and unchanging since age 6 weeks. Ophthalmologic exam at She had nasal tone. Her philtrum was short, her nares
age 4 years best corrected visual acuity of 20/40 in each eye. She anteverted, and she had an attached frenulum of the upper
was wearing bifocals of
1.50 þ1.25 axis 90 in each eye with lip. No other dysmorphic features were noted.
mild mixed astigmatism. Although clycloplegic drops (1% Review of the family history showed that the parents are
nonconsanguineous and of English and Scottish ancestry. The
proband has two older sisters who are normal. The proband’s
father has a history of asthma and adult onset epilepsy. The
maternal grandmother had spinocerebellar ataxia of an un-
*Correspondence to: Ahmad S. Teebi, MD, Division of Clinical known type. There is no family history of developmental delay
and Metabolic Genetics, The Hospital for Sick Children, 555 or heart defects. No other relatives had fixed large pupils
University Avenue, Toronto, Ontario M5G 1X8, Canada. although a paternal cousin had low vision and eyes that
E-mail: ahmad.teebi@sickkids.ca ‘‘jumped all over,’’ presumably nystagmus.
Received 21 November 2003; Accepted 11 June 2004 Our proband exhibits both of the features described in the
DOI 10.1002/ajmg.a.30341 cases of Buys et al. [1993] and Graf and Jungherr [2002]

ß 2004 Wiley-Liss, Inc.

 Research Letter 319

(congenital mydriasis and patent ductus arteriosus), as well as REFERENCES

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unilateral dilation of the ureter and renal calyces, and congeni- mydriasis. Abstract. J Am Ass Ped Ophthalmol Strab 8:102.
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present in their first child. There appears to be involvement of and patent ductus arteriosus. Arch Ophthalmol 120(4):509–510.
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may represent a more severe form of this association, ex- J.R. Buncic
tending its spectrum beyond association with PDA, or just a Shelley J. Kennedy
fortuitous association of the described anomalies. It is more Sarah J. Dyack
likely, however, due to the nature of the defects, that the Ahmad S. Teebi*
constellation of findings represents a previously unrecognized Division of Clinical and Metabolic Genetics
syndrome where congenital mydriasis and patent ductus and Department of Ophthalmology
arteriosus are the minimal components. More reports are The Hospital for Sick Children
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