Thurston Syndrome: An Insight of a Rare Case and Literature Review

ABSTRACT

This article reports an infant presented with multiple congenital abnormalities, which is considered a rare case. A 2-month-old girl presented with cleft palate, lobulated tongue, frontal bossing, postaxial polydactyly of hands, and other clinical manifestations involving oral, facial, and digital malformations. Hence, a provisional diagnosis of oral-facial-digital syndrome (OFDS), a rare genetic disorder, was contemplated. A genetic test was undertaken, and a confirmatory diagnosis of OFDS type-V (Thurston syndrome) was made. A brief description of the case and literature review of OFDS, including various aspects like etiology, inheritance, clinical features, and management, are discussed here.

How to cite this article

Sreekumar D, Dutta B, Dhull KS, et al. Thurston Syndrome: An Insight of a Rare Case and Literature Review. Int J Clin Pediatr Dent 2024;17(2):206–210.

Introduction

Genetic syndromes are anomalies resulting from the mutation in an individual's genome.¹ Few of these comprise clinopathy syndromes, a group of rare Mendelian disorders that originate from dysfunction in the primary cilium that aids in desired organ patterning and growth.² Oral-facial-digital syndrome (OFDS) is a group of unusual clinopathies that affect the development of the oral cavity (mouth, tongue, teeth, and jaws), face (head, eyes, and nose), and digits (fingers/toes). Common clinical findings encompass a cleft in the palate, lobulated tongue, broad flat nasal bridge, and widely spaced eyes (hypertelorism). Abnormalities in digits include fusion of certain fingers/toes (syndactyly), shorter digits (brachydactyly), or the presence of extra digits (polydactyly).³

The first case of OFDS was reported by Mohr in 1941 and was subsequently named OFDS II.⁴ An X-linked dominant condition exclusively affecting females was identified by Papillon-Léage in 1954, and although it was reported after Mohr, it was classified as OFDS I for some unknown reason.⁴ Torellio, in 1993, broadened the phenotypic spectrum of OFDS, which engendered its new types.³ To date, researchers have identified at least 19 potential forms of OFDS based on their pattern of presentation; however, the features of various types overlap significantly.^5,6 The prevalence of OFDS, as reported, ranges between 1:50000 to 1:250000 childbirth, and type-I accounts for the majority of cases in this disorder.⁷ The other forms are rare, and very few cases have been reported to date.

Case Description

A girl child aged about 2 months was referred from the Department of Pediatrics for oral consultation. The chief complaint was difficulty in feeding, nasal regurgitation, and some nodule-like structures under the tongue since birth. On general examination, she presented with fever, cough, and wheezing, which indicated possible signs of respiratory tract infection. The general clinical features observed were frontal bossing, hypertelorism, and depressed nasal bridge (Fig. 1A). The hands exhibited postaxial polydactyly (Fig. 1B). The ears are low set and a spherical depression was observed on the back of her head, indicating possible hypoplasia of the cranial base (Fig. 1C). Intraoral examination revealed cleft in the soft palate, lobulated tongue, and serrated mandibular arch. A subtle midline lip defect in the upper lip was also noted (Fig. 2).

Figs 1A to C:

(A) Hypertelorism, frontal bossing, and depressed nasal bridge; (B) Postaxial polydactyly of hands; (C) Spherical depression on the back of the head, low set ears

Figs 2A to D:

(A) Veau's class 1 cleft palate; (B) Tongue nodules/tongue hamartomas, midline lip defect in the upper lip; (C) Serrated mandibular arch; (D) Abnormal gums

Family history revealed the consanguineous marriage between parents. The pregnancy was uneventful, although the delivery was cesarean. Prenatal history does not suggest any radiation exposure or intake of medications during pregnancy except those prescribed by a doctor.

Investigations and Diagnosis

A provisional diagnosis of OFDS I was made, and DNA testing was advised. A homozygous mutation in the DDX59 (615464) gene on chromosome 1q32 was illustrated, and hence, the final diagnosis of OFDS type-V was made (Fig. 3).

Fig. 3:

Report of genetic testing confirming OFDS type V

Management

Case management included counseling of the parents and treatment as per the complaint.

Genetic counseling was provided to the parents regarding the frequency (25%) of expression of this disorder with each pregnancy. They were also educated about the possible sequelae of the syndromic malformations and the need for periodic dental care/management in the future.

The immediate treatment plan was the fabrication of an obturator to facilitate feeding and prevent nasal regurgitation of the milk. Elastomeric impression material was used on a custom tray to register the final impression of the upper arch (Figs 4A to C). Cast was poured with a die stone (Fig. 4D). The feeding plate was fabricated using self-cured resin material (Fig. 4E). It was then inserted into the patient's mouth following finishing, intraoral adjustment, and polishing (Fig. 4F). Mother was also educated on the use of feeding plate and the method of bottle feeding in an upright position (Fig. 5). They were asked to report after 1 week for the follow-up. No nasal regurgitation was observed during the follow-up, and the patient's mother was happy. As a permanent solution to the existing problem, it was advised to undergo surgery of the child at a later stage for the treatment of the cleft palate and the tongue hamartomas. The importance of periodic dental visits and speech therapy was also warranted.

Figs 4A to F:

(A) Special tray selection; (B) Cast poured; (C) Impression taking; (D) Final impression; (E) Fabrication of obturator; (F) Obturator after finishing and polishing

Fig. 5:

Feeding with the obturator

Discussion

The etiology of OFDS has never been clear. The causative genes have not been identified for 40% of the cases.⁸ The first gene known to be associated with this group of syndromes is OFD1. Type-I is inherited in an x-linked dominant pattern, although most other forms, including OFDS-V, are autosomal recessive in nature, which suggests that both the parents carry one copy of the mutated gene, but none of them have any manifestation. OFDS-V is caused by a homozygous mutation in the dead box polypeptide 59 gene DDX59 (615464) on chromosome 1q32.⁹

The OFDS-V is one of the mildest forms of OFDS. Thurston, in 1909, reported the first incidence of a case in a 20-year-old recruit in Bengal police; thus, this anomaly was named Thurston syndrome and later classified as OFDS-V.¹⁰ A landmark book titled Treasury of Human Inheritance, published in the year 1897, detailed similar cases by Roux of two brothers with median cleft lip and hexadactyly. Later, referring to his case, Rischbieth, in 1910, in the next volumes (volumes 6 and 7) of this book, reported the presence of postaxial polydactyly and median cleft of the upper lip.¹¹ Similar patient profiles have been detailed by Khoo and Saad,¹² Gopalakrishna and Thatte,¹³ Christophorou and Nicolaidou,¹⁴ and Burian¹⁵ Jain and Singh in 2019 revealed that only 13 cases have been reported on OFDS-V and the majority of them were of Indian descent.¹⁶ According to Salerno et al., in 2021, rare genetic syndromes will have a global prevalence of 40 cases in 100,000 people.¹

Unlike other types, OFDS-V has its unique characteristics of subtle upper midline lip defect, which is seen in almost all of its cases. Some patients with Thurston syndrome may also exhibit clinical manifestations like bifid uvula, duplicated frenulum, enamel hypoplasia, and anomalies in tooth numbers.¹⁷ Provisional diagnosis of OFDS-V can also be made by assessing the intelligence level of the patient. While other forms of OFDS display a low level of intelligence due to the involvement of the central nervous system, OFDS-V patients show normal intelligence.^17,18 The case presented here is probably the youngest among all the cases of OFDS reported to date. Radiological and intellectual assessment of this case was not feasible owing to the age factor. Hence, the diagnosis of OFDS-V was confirmed based on the genetic test.

Conclusion

It is necessary to emphasize the early recognition of anomalies that compound a syndrome, enabling a final diagnosis. Dentists should be able to help in achieving the diagnosis of rare syndromes that have oral manifestations as it can render a prognosis to the parents of the child.