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Title:

THURSTON SYNDROME: Oral and systemic manifestations. Case report and review of literature

Dr. Venkatesh G Naikmasur

M.D.S.

Professor & Head, Department of Oral Medicine and Radiology Sri Dharmasthala Manjunatheshwara College of Dental Sciences & Hospital, Dharwad Karnataka – 580 009, India. Email : [email protected] FAX NO: +918362467612

Dr. Arpita Rai

(M.D.S).

Post Graduate student, Department of Oral Medicine and Radiology Sri Dharmasthala Manjunatheshwara College of Dental Sciences & Hospital, Dharwad, Karnataka- 580 009, India. Email : [email protected] FAX NO: +918362467612

Dr. Manjunatha M. Revanappa (M.D.S). Post Graduate student, Department of Oral Medicine and Radiology Sri Dharmasthala Manjunatheshwara College of Dental Sciences & Hospital, Dharwad, Karnataka- 580 009, India. Email : [email protected] FAX NO: +918362467612 Dr. Sunil Mutalik M.D.S. Assistant Professor, Department of Oral Medicine and Radiology Sri Dharmasthala Manjunatheshwara College of Dental Sciences & Hospital, Dharwad, Karnataka- 580 009, India. [email protected]

FAX NO: +918362467612

ABSTRACT Oral-facial-digital (OFD) syndrome is a generic name for a variety of different but possibly related genetic disorders that result in malformations of the mouth, teeth, jaw, facial bones, hands and feet and are therefore categorized under oro-acral disorders. 9 different subtypes of OFD syndromes have been identified. OFD Type V is known as Thurston syndrome of which only 11 cases have been reported so far. We report a case of 19 year old male with this syndrome. A brief review of previously reported cases and discussion of anomalies of the syndrome is presented.

KEYWORDS Thurston syndrome, Oro-facial-digital Syndrome, Median cleft lip, Postaxial polydactyly, Oro – acral, Autosomal recessive.

INTRODUCTION Oro-facial-digital syndromes (OFD) are a group of congenital abnormalities categorized under Oro-acral disorders1. 9 different subtypes of OFD syndromes have been identified2. Common to all are minor facial anomalies, oral findings and digital anomalies. OFD Type V is known as Thurston syndrome. Thurston in 1909 was the first to report the presence of postaxial polydactyly with median cleft of upper lip, in a Hindu family3. Oral manifestations of Thurston syndrome include enamel hypoplasia, hypodontia, hyperplastic frenula, supernumerary teeth and highly arched palate4. The relative rarity of this syndrome can be assesed from the fact that only 11 cases of this syndrome have been published so far in world literature. One interesting finding about the syndrome is that with the exception of 2 cases, all subjects were of Indian descent4. We report a case of Thurston syndrome in a 19-year-old Indian male who presented with oral features, median cleft of upper lip and polydactyly of both hands and feet. CASE REPORT A 19 year old Indian male, reported to the Department of Oral Medicine and Radiology, for thermal sensitivity of teeth since one month. Patient was one of the three siblings of non consanguineous parents with no family history of orofacial or acral malformations. He was moderately built, well nourished and appeared to have normal intelligence. Routine general physical examination revealed an extra finger in both hands in the postaxial position (Figure 1). While the extra digit in left hand was a well formed articulated digit (presenting as Type A of Temtamy and McKusick classification5), the one in the right hand appeared rudimentary (Type

B5). Postaxial polydactyly was observed in both feet (Figure 1) presenting as sixth ray duplication (Watanabe et al6). No functional deficit in relation to hands or feet was noticed. On extra oral examination, midline cleft of the upper lip (Figure 2) was seen which extended till the vermilion border. Intra – orally multiple missing permanent teeth (41,32,33,34) and a number of retained deciduous teeth (53,72,73,74,81) were noted. 16,26,37,47 were decayed and 73, 74, 75 had cervical abrasion, which could be attributed to patient’s chief complaint. 31 was rotated distolingually. All dental findings were confirmed by orthopantomogram (Figure 3). Presence of double freni in lower labial vestibule was noted (figure 2). No associated tongue or palate anomalies were evident. Hand and wrist radiograph showed Type II postaxial polydactyly of right hand (presence of extra phalanges) and Type IV17(complete metacarpal duplication without carpal duplication) of left hand (Figure 4). Radiograph of feet (Figure 4) revealed presence of a Y- shaped metatarsal (one of the four metatarsal patterns of Venn – Watson morphological classification of polydactyly of feet8) in both feet. The diagnosis of OFD V was arrived based on presence of median cleft of upper lip, double freni, and bilateral post axial polydactyly of both hands and feet. Orthodontic consultation and opinion regarding surgical correction of upper lip was sought. Patient is currently undergoing treatment for functional & esthetic corrections.

DISCUSSION THURSTON SYNDROME or OFD V is well recognised as an autosomal recessive congenital condition, clinically presenting as post axial polydactyly, median cleft of upper lip,

duplicated frenulum and other oral manifestations. Since the first case of OFD V was reported by Thurston in 19093, only a few sporadic cases on this syndrome have been reported. Confusion exists over the incidence of this syndrome. A thorough survey of the English language literature encompassing PubMEd and Google Scholar search revealed 10 cases similar to that described by Thurston (Table1) Polydactyly is generally classified into three major groups: medial ray (preaxial), central ray and lateral ray (postaxial). Of the three types, postaxial polydactyly is encountered most frequently. Several classifications have been proposed in the literature to systematize this variable malformation, primarily based on morphology. Watanabe et al6 proposed a morphological classification of polydactyly of foot based on type of ray involvement and level of duplication. Lateral-ray polydactyly was divided into fifthray duplication (medial supernumerary toe) and sixth-ray duplication (lateral supernumerary toe). In Venn-Watson8 classification of postaxial four metatarsal patterns were noted: soft-tissue duplication, wide metatarsal head, Y-shaped metatarsal and complete duplication. In the present case, sixth – ray duplication was evident in both feet, on clinical examination with Y- shaped metatarsal bone seen bilaterally on anterio- posterior feet radiographs. Reports of polydactyly of the hand are numerous. According to Temtamy and McKusick 5 postaxial polydactyly is divided into types A and B. In type A the extra digit is well formed, articulates with the fifth or extra metacarpal and is inherited as a dominant trait with reduced penetrance. Type B is represented by a poorly differentiated extra digit, usually just a skin tag attached to the fifth finger. The inheritance of type B is unclear. The classification system followed by American society for surgery of hand7 is given in Table 2. Our case presented with type A polydactyly of left hand and type B polydactyly of right hand clinically which was later

confirmed as type IV 1 of left hand & type II of right hand respectively by hand and wrist radiographs. One other interesting finding of OFD V is frenulum duplication. Abnormal frena have been found associated with several genetic and chromosomal conditions, other than OFD syndromes, such as Ehlers-Danlos syndrome (EDS), infantile hypertrophic pyloric stenosis (IHPS), Ellisevan Creveld syndrome (EVCS) and holoprosencephaly18. Munke et al. noted oral frenula as a finding in Thurston syndrome19. Median cleft of upper lip is the other diagnostic feature of Thurston syndrome. Its incidence is about 1: 10,00,000 births and may occur as a sporadic event or as a part of an inherited sequence of anomalies such as DeMyer sequence or median cleft face syndrome.20 Close differential diagnosis for Thurston syndrome is OFD type VI which mimics this condition except for cerebellar anomalies and absence of oral frenula.21 Other OFD syndromes to be excluded in the differential diagnosis are OFD IV (Baraitser- Burn syndrome), OFD III (Sugarman syndrome), OFD I (Papillon-League-Psaume syndrome), and OFD II (Mohr syndrome).22 The diagnosis of Thurston syndrome can be easily made based on clinical and radiological findings. A brief knowledge of various limb anomalies is essential to diagnose this condition. Management of oral manifestations in these patients can be achieved by conventional treatment methods like orthodontic correction for alignment of teeth supplemented by extraction of over retained teeth. Surgical intervention for esthetic correction of median cleft of lip should be sought.

FIGURE

FIGURE 2

1

FIGURE 3

FIGURE 4

LEGENDS FOR FIGURES 1. FIGURE 1 – Postaxial polydactyly of both hands and feet 2. FIGURE 2 – Midline cleft of the upper lip 3. Figure 3 - Double frenula in mandibular labial vestibule. 4. FIGURE 4 – Orthopantomogram showing multiple impacted permanent teeth and

retained primary teeth. 5. FIGURE 5a – Hand and wrist radiograph showing Type II postaxial polydactyly of right

hand and Type IV1 polydactyly of left hand. 6. FIGURE 5b - Anterior – Posterior feet radiograph showing Y – shaped metatarsals of

both feet.

TABLE 1- SUMMARY OF DATA OF REPORTED CASES OF THURSTON SYNDROME CASE NO. 1

REPORTED BY

YEAR

MANIFESTATION

DESCENT

THURSTON3

1909

INDIAN

2

RISCHBIETH9

1910

3

BURIAN10

1962

4

CHAURASIA & GOSWAMI11

1973

5

CHOWDHARY12

1975

6

KHOO & SAAD13

1980

7

SIDHU & GREWAL14

1980

8

GOPALAKRISHNAN THATTE15 CRISTOPHOROU NICOLAIDOU 16

& 1982

Median cleft of upper lip, polydactyly Median cleft of upper lip, polydactyly Median cleft of upper lip, bilateral hexadactyly, reduplication of halluces Median cleft of upper lip, bilateral hexadactyly, Median cleft of upper lip, bilateral hexadactyly, Median cleft of upper lip,polydactyly, syndactyly, multiple toe anomalies Hypertelorism, cleft lip, Brachydactyly, syndactyly Median cleft lip, bilateral polydactyly, Non median cleft lip, Brachydactyly, syndactyly Cleft lip, polydactyly, Median cleft of upper lip, polydactyly,

9 10 11

PRAMOD KUMAR17 ASHIMA4

AND 1983 1988 2006

INDIAN NON INDIAN

INDIAN INDIAN INDIAN

INDIAN INDIAN NON INDIAN INDIAN INDIAN

TABLE 2 - CLASSIFICATION SYSTEM FOLLOWED BY AMERICAN SOCIETY FOR SURGERY OF HAND FOR POSTAXIAL POLYDACTYLY OF HAND Postaxial Polydactyly7 I Soft tissue II Extra phalanges III Two fingers on single metacarpal head IV Y shaped metacarpal IV1 Without carpal duplication IV Complete metacarpal duplication IV2 With associated carpal duplication

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