Journal of Medical Genetics 1988, 25, 41-43

Iris coloboma, ptosis, hypertelorism, and mentalretardation: a new syndromeM BARAITSER AND R M WINTERFrom The Hospital for Sick Children, Great Ormond Street, London WC]N 3JH; and The Kennedy-GaltonCentre, Harperbury Hospital, Radlett, Herts WD7 9HQ.

SUMMARY Two sibs and an unrelated single patient have a combination of iris coloboma, ptosis,hypertelorism, broad nasal bridge, short stature, and mental retardation. The LondonDysmorphology Database was used to determine whether this is a new syndrome.

The concept of a provisionally unique syndrome wasformulated by Cohen' in 1982 to describe theoccurrence in a single person of a syndrome that hadnot previously been reported. He suggested that itshould remain 'private' until other reportsappeared. He used the designation 'a pedigreesyndrome' to refer to a unique condition in a family.The reason for differentiating between the two wasto indicate that the pedigree syndrome was ofknown genesis whereas the provisionally private orunique syndrome could be either genetic or environ-mentally caused.

It is a commonplace occurrence for a so called'new' or 'private' syndrome to be subsequentlyfound in old, often obscure publications. If authorshad better access to old published reports it is likelythat many of the 'new' syndromes would be encoun-tered. One of the functions of the London Dysmor-phology Database is to allow the clinician rapidaccess to these reports so that clinically similar casescan be ascertained.2 We report two sibs and a thirdsingle case with an unusual combination of dysmor-phic features which could constitute a new auto-somal recessive syndrome.

Case reports

CASE 1

Case 1 was first seen when she was seven years ofage. She was born after a normal pregnancy tonon-consanguineous Asian parents. Her birthweight was appropriate for gestational age and therewere no perinatal problems. Her parents firstbecame concerned when she was not sitting at sixmonths and her development has been globallyretarded ever since. Now at the a,ge of seven years

Received for publication 13 Novembcr 1986.Revised version accepted for publication 16 December 1986.

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she can walk but she has no understandable speech.On examination her height was below the 3rd centilewhereas her head circumference was on the 25thcentile, as was her weight. She has bilateral ptosis,hypertelorism, a broad nasal bridge, and prominentepicanthic folds (fig 1). In addition, she has bilateral

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FIG 1 Case 1. Note the bilateral ptosis, hypertelorism, andepicanthus inversus giving an appearance of a broad nasalbridge.

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iris colobomata. The rest of the examination wasentirely normal.

CASE 2Case 2, the younger brother of case 1, has a similarhistory. He is globally retarded. His height is belowthe 3rd centile, and he has bilateral iris colobomata,ptosis, and prominent epicanthic folds with inferiorepicanthus which gives the impression of a broadnasal bridge (fig 2). All investigations includingthyroid function and chromosomes were normal.

CASE 3Case 3 was born by caesarean section and weighed3-6 kg at birth. She has a normal older sister and herparents are unrelated Caucasians. At seven monthsof age the parents first became anxious by theirdaughter's developmental delay and by her unusualappearance. When seen at that stage she was foundto have a skull circumference on the 10th centile anda height below the 3rd centile. Her face wascharacterised by a metopic ridge, broad nasalbridge, bilateral ptosis, and hypertelorism. She-hada left sided iris coloboma (fig 3). She was generallyhypotonic and globally delayed. She subsequentlysat unaided at 14 months and was able to pull herself

FIG 2 Sib of case 1.

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ia. .

Note the similar facial features.

FIG 3 Single patient with left sided iris coloboma, hyper-telorism, ptosis, and broad nasal bridge.

up on to furniture at 23 months; she had singlewords at 17 months. When seen at the age of fouryears the above, features were noted and, in addi-tion, she had a short neck and low posterior hairline.Her stature had remained short, below the 3rdcentile, and her development was still greatlydelayed. A chromosomal analysis with G bandingwas normal.

Discussion

The main clinical features in these three childrenwere the presence of colobomata of the iris, ptosis,telecanthus, hypertelorism, mental handicap, andshort stature. The nasal bridge appears wide,possibly because of the prominent inferior margin ofthe broad epicanthus. The cheeks are prominentand slope down to a pointed chin.Using the London Dysmorphology Database, no

conditions had a combination of iris coloboma,mental retardation, and ptosis. On using the com-bination of iris coloboma and mental retardation alist of 17 conditions were suggested, but none ofthese fitted. We considered CHARGE association3but two criteria (coloboma and retardation ofgrowth or development or both) are insufficient fora diagnosis. Joubert syndrome4 was also consideredas iris coloboma and mental retardation are two ofthe features, but these children did not show anunusual breathing pattern, nor did they have abnor-mal eye movements or a cerebellar ataxia. The shortstature, hypertelorism, ptosis, short neck, and low

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Iris coloboma, ptosis, hypertelorism, and mental retardation: a new syndrome

posterior hairline did lead us to consider Noonansyndrome5 in case 3 but, to date, colobomata of theiris have not been reported and the facial gestalt(figs 1, 2, and 3) is different.We present these three children to draw to the

attention of clinical geneticists a new autosomalrecessive syndrome.

References

Cohen MM. Syndrome delineation and its implications for thestudy of pathogenetic mechanisms. Advances in the Study ofBirth Defects. Vol 5. Lancaster: MTP Press, 1982:103-38.

2 Winter RM, Baraitser M, Douglas JM. A computerised data

base for the diagnosis of rare dysmorphic syndromes. J MedGenet 1984;21:121-3.

3 Pagon RA, Graham JM, Zonana J, Yong SL. Coloboma,congenital heart disease and choanal atresia with multipleanomalies: CHARGE association. J Pediatr 1981;99:223-7.

4 King MD, Dudgeon J, Stephenson JBP. Joubert's syndromeswith retinal dysplasia: neonatal tachypnoea as the clue to a

genetic brain eye malformation. Arch Dis,Child 1984;59:709-18.Allanson JE, Hall JG, Hughes HE, Preus M, Witt RD. Noonansyndrome: the changing phenotype. Am J Med Genet1985;21:507-14.

Correspondence and requests for reprints to Dr MBaraitser, Clinical Genetics Unit, The Hospital forSick Children, Great Ormond Street, LondonWC1N 3JH.

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