JrMed Genet 1998;35:435-437

Unknown syndrome: peculiar face, severehypodontia of permanent teeth, and precociouschoroid calcifications

Rosanna Pallotta, Paola Fusilli

AbstractWe describe a mother and her twindaughters affected with severe hypodontiaofthe permanent teeth, precocious calcifi-cation of the choroid plexus, and minordigital anomalies. The presence of innertelecanthus, broad and flattened nasalbridge, mild ocular proptosis, small nosewith anteverted nostrils, and slight micro-retrognathia gives them an unusual ap-pearance. All three affected persons are ofnormal intelligence.(JMed Genet 1998;35:435-437)

Keywords: oligodontia; persistent deciduous teeth;choroid plexus calcifications

Centre for Diagnosis,Prevention and Care ofBirth Defects inChildren, DepartmentofMedicine, Section ofPaediatrics, GD'AnnunzioUniversity, Chieti,ItalyR PallottaP Fusilli

Correspondence to:Professor Palotta, Piazzadella Rinascita 75, 65122Pescara, Italy.

Received 30 October 1997Revised version accepted forpublication11 November 1997

Both hypodontia and anodontia are well knowndisorders. Complete anodontia is very rare;according to Bartsocas,' Pyrrhus (318-272BC), King ofEpirus, may have been affected. Itis inherited as an autosomal recessive trait.2Witkop' suggested that the trait of small, peg

shaped, or missing maxillary lateral incisors notassociated with a syndrome is best explained asan autosomal dominant trait modified by apolygenic component, and that agenesis ofsuccedaneous teeth is a recessive trait thatresults from the homozygous state of this gene.4Dolamore' described a case of persistentdeciduous canines with absence of permanentsuccessors. Gorlin (personal communication)pointed out that about a third of the generalpopulation lack one or more of the third molars(wisdom teeth), the teeth most often missing,followed by the premolars. Anodontia and

hypodontia are often the expression ofcomplexsituations involving defective formation ofstructures of ectodermal origin.We describe a family who have, to our

knowledge, a completely new condition.

Case reportWe report a family which includes a 39 year oldaffected mother and her 20 year old twindaughters. At the time of conception theirfather was 24 years old. They are of southernItalian origin, their mother, the third of fivechildren (three males and two females), comingfrom Sicily and their father, the second of threebrothers, from Abruzzo; the parents are notrelated. The family history on both sides wasnegative for miscarriages, malformations, andgenetic or metabolic disease. The girls wereborn at 31 weeks of gestation and wereregistered as monochorionic identical twins.Their growth was appropriate for age (90thcentile), they were negative for transplacentalinfections (TORCH), and their psychomotordevelopment was absolutely normal. Theblood group of all three patients was 0Rh(D)+. They came to our attention at the ageof 12 years through genetic counselling. Theirearly medical history, like that of their mother,was unremarkable; growth parameters werestill around the 90th centile and their intelli-gence was well above average.The twins' faces showed very similar charac-

teristics to that of their mother (figs 1,2, and 3),although more accentuated, and included innertelecanthus (ICD >97th centile, IPD >95thcentile, OCD >75th centile), downward slantingpalpebral fissures, mild ocular proptosis, flat-tened, wide nasal bridge, a small nose withforward slanting nostrils, slight microretrog-nathia, and severe oligodontia of the permanentdentition, the upper central incisors (11,21) andfirst molars being present (16, 26, 36, 46) withpersistence of the remaining deciduous teeth.The resulting dental formula was:

55 54 53 5211 21

62 63 64 65

85 84 83 82 81 71 72 73 74 75

Figure 1 Front view of the girls at 12 years of age.

Furthermore, questionable loss of the inter-dental vertical dimension, full lips, pectus cari-natum, clinodactyly of the fifth finger, andhypoplastic distal phalanx of the second toewere observed. The mother had a right singletransverse palmar crease.

In all three family members, cranial radio-graphs showed two bilateral and symmetrical,

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Pallotta, Fusilli

Figure 3 The mother.

rounded, calcified masses (fig 4, top row)apparently localised at the level of the basalganglia, hypoplastic greater wings of the sphe-noid, narrowed, cribriform plate of the eth-

moid bone, fused clinoid processes, hypoplasticnasal septum, and agenesis of all permanentteeth, except for the upper middle incisors andfirst upper and lower molars. These findingswere all confirmed three months later on CTscan, except for the large calcifications, whichwere situated at the level of the choroid glomus(fig 4, bottom row) but not accompanied bysigns of intracranial hypertension. The meta-carpophalangeal profile (MPP) showed someshortening of all the second phalanges, moreaccentuated in the fifth finger. X rays also con-firmed the shortening of the distal phalanx ofthe second toe. The remaining skeletal, oph-thalmological, and cardiac examinations werenormal.

Dermatoglyphic analysis showed: (mother)right: Wd, Wd, Wd, W, W; palmar a-b ridgecount (a-b)=40; atd=40'; total finger ridgecount (TFRC)= 148; mainline formula=11.9.7.5".13" t, left: Wd, Lr, Wd, Wd, Ur;a-b=43; aid=40'; TFRC=130; mainlineformula=9.7.5".5'.13'-t. (1st girl) right: Lu,Ur, Lu, W, Wd; a-b=44; aid=47°; TFRC=97;mainline formula=ll. 9.7.5'.13'-t, left: W, Ur,Uz, W, W; a-b=37; atd=43°; TFRC=107;mainline formula= 9.9.5".5'. 13'-t. (2nd girl)right: Wd, UL, A, Wd, Wd; a-b=40; aid=440;TFRC=97; mainline formula=l1. 9. 7. 5'.13'-t, left: Wd, Ur, Ur, W, Wd; a-b=43;atd=440; TFRC=93; mainline formula= 1. 9.7. 5'. 13'-t.

Direct counting of the patients' sweat poresin different areas of the palm and fingers wasnormal. The karyotype was normal. In spite ofthe absence ofany neurological or bone densityabnormality, the intracerebral calcifications ledus to perform several laboratory tests, includ-ing calcium and parathormone level, which allproved to be normal.We followed up the family for over eight years.

During this period nothing of particular clinicalinterest was observed. The problem of the den-tal anomalies was solved by extracting thedeciduous teeth and applying a permanentprosthesis in the mother and by applying a

Figure 4 Calcifications of the choroid glomus in (A) the mother, (B) the first girl, and (C) the second girl. Top row: lateral skull radiographs, bottom row:cranial CT scan.

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Hypodontia and choroid calcifications

Table 1 Phenotype of the family: note that the expression of the gene defect is identical inall three subjects

Mother Ist girl 2nd girl

Inner telecanthus + + +Downward slanting palpebral fissures + + +Mild ocular proptosis + + +Flattened, wide nasal bridge + + +Small nose with forward slanting nostrils + + +Hypoplastic maxilla + + +Slight microretrognathia + + +Persistence of deciduous teeth + + +Permanent teeth: 11, 21, 16, 26, 36, 46 + + +Full lips + + +Pectus carinatum + + +Clinodactyly of the 5th finger + + +Hypoplastic distal 2nd phalanx of the foot + + +Hypoplastic wings of the sphenoid + + +Hypoplastic nasal septum + + +Agenesis of permanent teeth + + +High total finger ridge count + + +Bilateral choroid plexus calcifications + + +Mental retardation - - -

conservative prosthesis to the deciduous teeth inthe daughters. The growth parameters haveremained on the 90th centile. School resultsconfirmed the high intelligence level of thetwins.

DiscussionAlthough the twins had been referred to at

birth as monochorionic and identical, we alsoperformed the following: dermatoglyphicanalysis,6 blood groups, the Goldsmith twinsimilarity questionnaire,' and the ponderal index(Pondex).8 The conclusions drawn from all theresults were consistent with monozygosity.The patients reported here showed not only

dental abnormalities (the permanent teethconsisting merely of the upper central incisorsand first molars with persistence of theremaining deciduous teeth), but also ocularproptosis resulting from malformations of thesphenoid and ethmoid and hypoplasia of thenasal septum. These anomalies, together withthe inner telecanthus and full lips, give them aquaint, flat profile. The bone anomalies of thelimbs are not typical, consisting of clinodactylyof the fifth finger, hypoplasia of the terminalphalanx of the second toe, and shortening ofthe second phalanx of the fingers at the MPP.The total finger ridge count in the mother was

283, in the first twin 204, and in the second 204,all high values compared to the average 143.17of a female population in southern Italy.9As shown in table 1, the expression of the

gene defect is identical in all three subjects.The bilateral and symmetrical calcifications ofthe choroid glomus were very interesting. Thelatter were already evident when the girls were12 years old and, judging by their size, whichwas more or less the same in the daughters andmother, were presumably present long beforethe age of 10 years; they were bilateral andsymmetrical.

Similar calcifications may also be found inmetabolic diseases, such as pseudohypopara-thyroidism.'0 Although the cyclic AMP afterinfusion of exogenous parathormone in serumwas not measured because of the unavailabilityof this hormone, the suspected hypoparathy-roidism or pseudohypoparathyroidism was

excluded by the absence ofbiological or clinicalsigns, including the skeletal anomalies.

In the absence of any clinical pathologicalsigns, the calcifications of the choroid glomusin all three patients may be consideredphysiological. Calcifications with similar char-acteristics in the first decade of life have eithernot been found at all" or very rarely, in O.5%. 2It is well known that although these formationscan occur as early as the first three years of life,they are very uncommon in patients under theage of 10.12

It is an established fact that familial calcifica-tions of the choroid plexus are present in somegenetic diseases.'21' However, a thoroughreview, using computerised dysmorphologydatabases (both London and POSSUM), didnot show any association of choroid glomuscalcifications with hypodontia or facial anoma-lies or both that was similar to the features inour family.To our knowledge, oligodontia with persist-

ence of the decidous teeth and intracerebral cal-cifications has so far only been reported once,'4in two daughters of a consanguineous marriageshowing the typical onion skin phenomenon,pathognomonic oflipoid proteinosis. The condi-tion presented here is clearly different.Thus, in spite of follow up lasting over eight

years and in the absence of other similar cases,only a familial factor or possibly a new malfor-maiion syndrome, clearly of autosomal domi-nant inheritance, can be proposed.

We are grateful to Professor Francesco Schioppa (Departmentof Biomedical Sciences, University of Chieti, Italy), who helpedin assessing monozygosity by statistical analysis, and to Dr LedaDalpra (Department of Biology and Genetics for MedicalSciences, University of Milan, Italy), who performed the karyo-typing of the patients.

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2 Gorlin RJ. Total absence of the permanent dentition: an auto-somal recessive disorder. Am J Hum Genet 1979;31:72A.

3 Witkop GJ Jr. Studies of intrinsic disease in isolates withobservations on penetrance and expressivity of uncertainanatomical traits. In: Bruzansky S, eds. Congenitul anomaliesof the face and associated structures. Springfield, IL: C CThomas, 1961:291-368.

4 Witkop GJ Jr. Agenesis of succedaneous teeth: an expressionof the homozygous state of the gene of the pegged or miss-ing maxillary lateral incisor trait. AmJMed Genet 1987;26:431-6.

5 Dolamore WH. Absent canines. Br DentJ 1925;46:5-8.6 Reed T, Sprague FR, Kang KW, Nance WE, Christian JC.

Genetic analysis of dermatoglyphic pattern in twins. HumHered 1975;25:263-75.

7 Spitz E, Moutier R, Reed T, et al. Comparative diagnoses oftwin zygosity by SSLP variant analysis, questionnaire, anddermatoglyphic analysis. Behav Genet 1996;26:55-63.

8 Likken DT. The diagnosis of zygosity in twins. Behav Genet1978;8:437-73

9 Pallotta R, Carlone G, Petrucci A, Chiarelli F. Derma-toglyphics in von Recklinghausen neurofibromatosis. Am JMed Genet 1989;34:233-6.

10 Smit L, van-Wiyk RM, Rico RE, Sitalsing AD. Intracerebralbilateral symmetrical calcifications, demonstrated in apatient with pseudohypoparathyroidism. Clin Neurol Neuro-surg 1988;90: 145-50.

11 Kwak R, Takeuchi F, Ito S, Kadoya S. Intracranialphysiological calcification on computed tomography. Part2. Calcification in the choroid plexus of the lateralventricles. No To Shinkei 1988;40:707-1 1.

12 Modic MT, Weinstein MA, Rothner AD, Erenberg G,Duchesneau PM, Kaufman B. Calcification of the choroidplexus visualized by computed tomography. Radiology1980;135:369-72.

13 Singh B, Jamil A, Al-Shahwan SA, Sharif H, Al-Deeb SM,Biary N. Choroido-cerebral calcification syndrome withretardation. Neurology 1993;43:2387-9.

14 Oezarmagan G, Baykal C, Gursoy EO, Yilmazer S,Buyukbabani N, Coban 0. Lipoid-proteinose bei zweiSchwestern. Hautarzt 1993;44:315-18.

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