Case reports

resembling those of SLO syndrome, especially whenatypical clinical or developmental signs are present.Although limitations in our diagnostic abilities exist,when patient's presentations do not conform toestablished descriptions of clinical syndromes, anexhaustive search for other aetiologies must bemade.

The authors wish to thank Ms Regina Kobli forexpert assistance in the preparation of this manu-script.

References

Smith DW, Lemli L, Opitz JM. A newly recognized syndromeof multiple congenital anomalies. J Pediatr 1964;64:210-7.

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2 Johnson VP. Smith-Lemli-Opitz syndrome: review and report oftwo affected siblings. Z Kinderheilkd 1975;119:221-34.

3 Lowry RB, Yong SL. Borderline normal intelligence in theSmith-Lemli-Opitz (RSH) syndrome. Am J Med Genet1980;5: 137-43.

4 del Solar C, Uchida IA. Identification of chromosomal abnor-malities by quinacrine-staining technique in patients withnormal karyotypes by conventional analysis. J Pediatr1974;84:534-8.

Correspondence and request for reprints to Dr AlanE Donnenfeld, Department of Clinical Genetics,The Children's Hospital of Philadelphia, 34th andCivic Center Blvd, Philadelphia, Pennsylvania19104, USA.

Incontinentia pigmenti in a boy with Klinefelter's syndromeA D ORMEROD*, M I WHITE*, E McKAYt, AND A W JOHNSTONt*Department ofDermatology, Aberdeen Royal Infirmary; tDepartment of Paediatrics, Royal AberdeenChildren's Hospital; and 4Department ofMedicine, University ofAberdeen, Aberdeen AB9 2ZB.

SUMMARY A boy with the cutaneous lesionsof incontinentia pigmenti is described.Chromosomal analysis revealed the 47,XXYkaryotype of Klinefelter's syndrome. Sinceincontinentia pigmenti trait is usually lethal inmales, the possibility of the second X chromo-some protecting against fetal death is discussed.

It has been suggested that the pattern of inheritanceof incontinentia pigmenti (IP) best fits that of an Xlinked dominant trait which is lethal in males.' 2Nonetheless, male cases have been recorded andconstitute 2 to 3% of all reported cases.1 2 All buttwo of these male cases occurred as sporadic newmutations. We describe a patient with incontinentiapigmenti and Klinefelter's syndrome, a combinationwhich has only been previously reported once.3

Case report

A boy aged one year presented to the DermatologyClinic with a history of linear, whorled, macular,streaky pigmentation predominantly over the rightside of the trunk but also extending on to one leg(figure). This was noticed in the first month of life

Received for publication 5 April 1986.Accepted for publication 7 May 1986.

but was not present at birth. No preceding inflamma-tory, vesicular, or warty skin eruption was observedby the parents or any of the baby's medicalattendants.At birth he was light for dates (2050 g at 41 weeks'

gestation). Neonatal blood films showed no evi-dence of eosinophilia. At his 18 month assessmenthis weight and head circumference were below the3rd centile. He was noted to have small epicanthicfolds, low set ears, elfin facies, and his skull waswider posteriorly than anteriorly, but psychomotordevelopment was normal. As his testes were smalland soft, Klinefelter's syndrome was suspected andchromosome analysis revealed a karyotype of47,XXY. He was assessed again at the age of twowhen he had developed conical, hypoplastic canineteeth. However, his hair was normal and his eyeswere normal apart from a transient strabismus.

His father was aged 29 at the birth of the child andhis mother 26. They were both Caucasian and werenot related. His mother had had one previouspregnancy which spontaneously aborted after 12weeks' gestation. Both parents were examined fullyand neither had any sign of pigmentary disturbance,its residual changes, or other features of incon-tinentia pigmenti. The mother's teeth were normaland both parents had normal karyotypes. Xg(a)blood groups were carried out by Dr Tippett on theproband and his parents. All were Xg(a-).

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Case reports

URE Pigmentation on trunk ofproband.

Discussion

This patient has skin changes typical of the pigmen-tary phase of IP. The pigmentary phase is the mostconstant sign of the syndrome and is not necessarilypreceded by vesiculation or verrucous changes,which were absent in 10*7% and 23-8% of cases,respectively, in a collected series.2 Apart from hisresolving strabismus and the dental defect, he has noother stigmata associated with IP at present.

Statistical analysis of 74 sibships supports thetheory that IP has an X linked dominant inheritancewhich is lethal in males.2 However, male patientsoccur sporadically (2 to 3%) and most are believedto represent new mutations, since only two reportsof affected males born to affected mothers havebeen found.4 5 How these males escape the post-ulated lethal effects of the abnormal gene is un-known, but those that survive are no more severelyaffected than their female counterparts.2 The possi-bility of this being due to a half chromatid mutationhas been debated,' 4 6 but another possible explana-tion has been the suggestion that affected males mayhave Klinefelter's syndrome or XX/XXYmosaicism.i Few of the reported male patients havehad their testes examined, which provided the cluehere, and few have had their karyotypes checked.There is only one previous report of XXY Kline-felter's syndrome in incontinentia pigmenti.3 Thereare reports of normal XY karyotypes, but in thesepatients Klinefelter mosaicism cannot be excluded. ' 6

It is tempting to speculate that the presence of anadditional X chromosome protected the patientfrom the lethal effects of the IP gene as it is thoughtto in females. This would apply whether the patientrepresented a new mutation or inherited the IP geneon the X chromosome from his mother.

To be protective the additional X chromosomewith a presumed normal allele would require to bederived by non-disjunction in the first meioticdivision of either spermatogenesis or oogenesis.Alternatively, the new mutation could have occur-red in one chromatid at the second meiotic divisionof oogenesis followed by non-disjunction. Unfortu-nately, Xg(a) blood grouping did not provideinfort--ation as to the source of the additional Xchromosome.Hodgson et al7 recently reported two girls with

IP and both showed balanced de novo X;autosometranslocations involving band Xpll. They thereforesuggested that this band might be the site of the IPgene locus. They also noted that the normalX chromosome was inactivated and discussedexplanations as to why the IP gene had not provedlethal.Wieacker et at8 showed that fibroblasts grown fromnormal and pigmented areas of skin contained thesame X chromosome. They suggested that thissupported the hypothesis that the transition frominflammation to hypertrophy could reflect normalcells replacing the defective ones expressing themutant allele by means of somatic selection againstthe defective cells. This theory would apply to thetwo X chromosomes of Klinefelter's syndrome.Chromosome analysis of other males with the

syndrome, with exclusion of mosaicism, may clarifythe inheritance of the disorder. The new recom-binant DNA methods should, when sufficientprobes are available, allow proof of the mode ofinheritance.

We should like to thank Dr P Tippett of the MRCBlood Group Unit, The Galton Laboratory,London, for the Xg(a) blood groups.

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Case reports 441

ReferencesHecht F, Hecht BK. The half chromatid mutation model andbidirectional mutation in incontinentia pigmenti. Clin Genet1983;24: 177-9.

2 Carney RG. Incontinentia pigmenti-a world statistical analy-sis. Arch Dermatol 1976;112:535-42.

3 Kunze J, Frenzel UH, Huttig E, Grosse FR, Wiedemann HR.Klinefelter's syndrome and incontinentia pigmenti. Block-Sulzberger. Hum Genet 1977;35:237-40.

4 Hecht F, Hecht BK Austin WJ. Incontinentia pigmenti inArizona Indians including transmission from mother to soninconsistent with the half chromatid mutation model. Clin Genet1982;21:293-6.

5 Kurczynski TW, Benns JS, Johnson WE. Studies of a familywith incontinentia pigmenti variably expressed in both sexes. JMed Genet 1982;19:447-51.

6 Langenbeck U.Transmission of incontinentia pigmenti frommother to son is consistent with a half chromatid back mutation(reversion) model. Clin Genet 1985;22:290-1.

7 Hodgson SV, Neville B, Jones RWA, Fear C, Bobrow M. Twocases of X/autosome translocation in females with incontinentiapigmenti. Hum Genet 1985;71:231-4.Wieacker P, Zimmer J, Ropers H. X inactivation patterns in twosyndromes with probable X-linked dominant male lethal inheri-tance. Clin Genet 1985;28:238-42.

Correspondence and requests for reprints to Dr A DOrmerod, Department of Dermatology, Room 211,Aberdeen Royal Infirmary, Foresterhill, AberdeenAB9 2ZB.

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with Klinefelter's syndrome.Incontinentia pigmenti in a boy

JohnstonA D Ormerod, M I White, E McKay and A W

doi: 10.1136/jmg.24.7.4391987 24: 439-441 J Med Genet 

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