Hereditary Oro-facial Digital Syndrome Type 1: Diagnosis and Management-case Report
Arun M. Xavier,
Amitha M. Hegde
Oral-facial-digital syndrome type 1 (OFD1) is characterized by an X-linked dominant mode of inheritance with lethality in males. It presents with peculiar malformations in the oral cavity and defects in the face and digits of the upper and lower extremities. Accurate diagnosis following clinical investigations by allied health professionals is indispensable to plan out a systematic management protocol in these victims in order to minimize future odontogenic problems. This report presented a unique case of females in a family suffering from manifestations of OFD1 syndrome since three generations. The characteristic clinical features of all the female members were promptly identified, investigated and the inter-disciplinary management protocol that was systematically instituted is depicted in this report.
Received: October 11, 2011;
Accepted: October 25, 2011;
Published: March 20, 2012
Oro-facial digital (OFD) syndrome is a generic name for a variety of different
genetic disorders that result in malformations of the oro-facial region and
digits (King and Sanares, 2002). Based on their distinguishing
physical signs, symptoms and mode of inheritance, several OFD syndromes are
enlisted in literature (Gorlin and Psaume, 1962; Gorlin
et al., 1961; King and Sanares, 2002). OFD1
is a pleiotropic disease crucially associated with dysfunction of the primary
cilia (Macca and Franco, 2009). Males with this condition
are mostly malformed fetuses delivered by women with OFD1 (Macca
and Franco, 2009).
The typical oral and peri-oral features of ODF1 include ankyloglossia, multi-lobulated
tongue with the presence of nodules, clefts of the alveolar ridge, multiple
hypertrophied frenula, cleft lip-palate, etc. (Mihci et
al., 2007). The facial abnormalities most commonly include aplasia of
the alar cartilage, ocular hypertelorism, strabismus and alopecia (King
and Sanares, 2002; Mihci et al., 2007). Brachydactyly,
syndactyly, clinodactyly of the fifth finger commonly, radial and ulnar deviation
and duplicated hallux (great toe) are some digital variations (Mihci
et al., 2007). Systemically debilitating conditions like polycystic
renal disease, sapasmodic movements/tics, brain malformation, delayed motor
and speech development may also be present in some patients (Gorlin
and Psaume, 1962; King and Sanares, 2002; Mihci
et al., 2007).
There is very limited documented dental literature regarding the oral manifestations of OFD1 syndrome and its clinical management in the Asian population. This report presents unique clinical cases of OFD syndrome with hereditary involvement among the female members of a family and the management protocol that was undertaken.
Two south Indian female siblings aged 9 and 12 years reported to the Department
of Pediatric Dentistry, A.B. Shetty Memorial Institute of Dental sciences, Mangalore
with a chief complaint of decay and malaligned teeth (Fig. 1a,
b, 2a, b). The children
were accompanied by their grandmother, mother and their youngest girl sibling
aged 5 years on the first day of visit.
The eldest sibling also complained of an enlarged tongue with noticeable swellings claimed to have increased in size since birth (Fig. 1c). A burning sensation on having hot and spicy food and pain upon palpating the swollen areas was also reported. Accompanying it, frequent bruising of the lateral borders of the tongue upon mastication, where the swellings were appreciably bigger in size was noticed. A detailed medical and family history was recorded and the patients were examined both clinically and radio graphically.
The 12 year old girl had a short stature (143 cm) with shorter upper and lower
limbs. The palm (Fig. 1d) and feet of either side (Fig.
1e) were typically small with shorter and wider digits, suggestive of brachydactyly.
The first toes in both the feet were larger than the others and resembled a
duplicated hallux. The patient was dolichocephalic, leptoprosopic with a convex
|| Clinical features of the 12-year old girl; (a) Anterior view
of malaligned dentition, (b) High arched palate, (c) Solitary tongue nodules
in the lateral borders, (d) Palms showing small digits and (e) Feet showing
|| Clinical features of the 9-year old girl; (a) Anterior view
of malaligned dentition, (b) High arched palate, (c) A nodular swelling
on the right dorsum of tongue and (d) A suggestive fibromatous mass on the
left lower lingual mucosa
Other extra oral facial features included a broadened forehead, base of nose
and widely set eyes. Alopecia was noted at the central portion of the head circumference.
Intraoral soft tissue examination revealed macroglossia with superficial and
inferior clefting of the anterior 2/3rd of the tongue. Solitary tongue nodules
of sizes 1.5x1 cm and lesser were noticed on the lateral borders of the tongue
bilaterally (Fig. 1c). The surface of the nodules was smooth,
featuring benign mass. Aplasia of papillae over the tongue was also a significant
finding. Hard tissue examination revealed clefting of the hypoplastic mandibular
alveolar process between 22 and 24 and 31 and 32 (Fig. 1a,
b), micrognathia, narrow constricted upper arch, high arched
palate (Fig. 1b), as the other striking findings apart from
decayed teeth and crowded dentition. Orthopantamograph showed the presence of
supernumerary teeth between 12 and 13 and missing teeth in relation to 23 and
All the permanent 1st molars were grossly decayed with pulpal involvement in the 9 year old sibling, with a huge pulp polyp in molar necessitating its extraction. The significant extra oral clinical findings in this 2nd sibling included a broadened forehead, flattened nasal bridge, bilateral downward slanting of the lateral canthi of eyes, a convex facial profile with incompetent lips. Intraorally, accessory frenulum, cleft involving the alveolar process in both the arches, a soft elevated non tender nodular swelling of 2x2 mM size in the right border of the middle 3rd of the tongue (Fig. 2c), narrow and constricted maxillary arch, high arched palate (Fig. 2b) and anterior open bite were the striking features. A 0.5 cm movable, non tender soft tissue fibrous mass, with well defined borders was noticed at the left lower part of the floor of the mouth (Fig. 2d). Orthopantamograph revealed the presence of a supernumerary tooth between 13 and 14, congenitally missing 32 and an impacted left upper lateral incisor.
|| Clinical features of the other family members 5-year old
sibling; (a) Clefting seen in the region of 42 and 43, (b) Duplicated hallux
(great toe) in the left leg, Mother, (c) Bifid tongue, (d) Syndactyly of
digits in the left hand, Grandmother, (e) Bifid tongue, (f) Abnormal bony
swelling in the right thumb and (g) Syndactyly of the great toe in the right
The extra-ordinary clinical presentation of similar extra and intra oral signs
in the siblings was suggestive of the possible occurrence of a genetic disorder/syndrome.
This urged the need for a thorough clinical examination of the other members
who had accompanied them from the family. To our surprise, all the 3 generations
had features that had similarities to great extent. Grossly decayed teeth and
enamel dysplasia were noticed in the youngest sibling and the members of the
other generations. The youngest sibling had clefting of the mandibular alveolar
process between 82 and 83 (Fig. 3a), a fibrous movable soft
tissue mass of 0.3x0.2 cm in the lingual gingival mucosa and widely set eyes.
A duplicated hallux (great toe) was also noticed in the left leg of the 3rd
sibling (Fig. 3b). Additionally, syndactyly of digits of either
upper or lower limbs (Fig. 3d-f), high arched
palate and bifid tongue (Fig. 3c-e) were
common to all the 3 of them.
The children were born to non-consanguineous parents and the mother reported
of uneventful pregnancies. The mother of these siblings admitted of no history
of abortions, male or still birth. The family history revealed that only the
maternal grandmother and mother suffered from similar clinical and dental conditions
and none of the grandmothers brothers or her sons had any visible/known
defect. The clinical and radiographic features and the family history were consistent
with a diagnosis of an X-linked dominant trait of OFD1 with female predisposition
and a pedigree chart of the familys condition was formulated (Fig.
The comprehensive treatment for OFD1 syndrome includes a wide array of measures,
as the clinical presentation of the same is diverse. As a part of the treatment
plan, the treatment alternatives were explained to the children and their mother.
Dietary counseling and education of maintenance of good oral hygiene were delivered.
|| Pedigree representation of OFD1 syndrome in the family
Root canal treatment was performed on all the permanent 1st molars that were
decayed and pulpally involved followed by placement of stainless steel crowns.
Light cure glass ionomer and composite restorations for decayed teeth following
excavation and cavity preparation was done. Extraction of root stumps, pit and
fissure sealants for teeth with incipient carious lesions etc. were also performed
in the siblings, according to their needs. The Department of Oral and maxillofacial
surgery undertook the surgical debulking of lipomatous swellings on the tongue
in the eldest sibling under general anesthesia. The malocclusion of the 9 and
12 year old sisters are being currently managed at the Dept of Orthodontics
and Dentofacial Orthopedics.
Surgical orthopedic correction of syndactyly/polydactyly in the other affected
members of the family was suggested. As a part of the treatment protocol, genetic
counseling to the family members was also provided.
The diagnosis of OFD1 is usually established at infancy based on characteristic
oral, facial and digital anomalies. A 50% risk of inheriting the disease causing
gene has been reported in children of females with OFD1. Most male fetuses of
an affected mother may fail to survive or lead to miscarriages (Ferrante
et al., 2001). This was however, not noticed in the family studied
in this report. The OFD1 gene is assigned to locations Xp 22.3-22.2, or, on
the 22nd band of the p arm of the X-chromosome (Ferrante
et al., 2001). The familial pattern of inheritance of this X linked
dominant trait in the females of the examined family, suggested a definite diagnosis
of Oro-facial-digital syndrome Type I. The diagnosis could have been confirmed
through molecular genetic testing of samples from all the family members, but
wasnt performed due to the patients unwillingness to participate.
A bifid or trifid tongue associated with nodules, usually hamartomatous or
lipomatous, is found to occur in 1/3rd the population with OFD1 (Sousa
and Kanaan, 1994; King and Sanares, 2002; Mihci
et al., 2007). Other common findings include ankyloglossia with short
lingual frenulae (King and Sanares, 2002; Mihci
et al., 2007). All the members of the current report presented with
bifid tongue and the 2 elder siblings presenting with characteristic nodular
swellings on the tongue surface.
Abnormalities in the palate including submucous cleft palate, trifurcation
of the soft palate, or high arched palate occur in more than half of this victimized
group (Al-Qattan, 1998; King and
Sanares, 2002). Hyperplastic accessory gingival frenula, extending from
the buccal mucous membrane to the alveolar ridge have found to result in alveolar
clefts or notching of the alveolar ridge in OFD1 (King and
Sanares, 2002; Mihci et al., 2007). Clefting
of the alveolar process of the jaw was only noticed in the 3 siblings of our
report, while high arched palate and bifid tongue was seen among all the female
The incidence of dental caries in the 3 generations was significant, the causes
being multifactorial (Motlagh et al., 2007; Zeraati
and Motlagh, 2006; Razafindrabe et al., 2007;
Ogundele and Ogunsile, 2008; Malekipour
et al., 2008). Understanding the exact etiology of dental decay and
instituting an individualized preventive or corrective strategy can lower the
caries prevalence in this high risk group (Mahvi et al.,
2006; Madukwe, 2007).
Digital abnormalities like duplicated hallux, brachydactyly and syndactyly
of varying degrees of severity was noticed in the present family, as was reported
in an earlier published report on OFD1(King and Sanares,
2002). Dry and brittle hair, usually accompanied by partial alopecia in
OFD1 syndrome (Del et al., 1999) was noticed
in the eldest sibling of the 3rd generation in this report. The short stature
in the eldest sibling maybe attributed to familial factors or a severe genetic
expression of this condition (Mohammadian and Khoddam, 2007).
In fewer than 50% of individuals with OFD1 syndrome, the occurrence of polycystic
kidney disease in later childhood or adulthood has served as a diagnostic marker
(Coll et al., 1997). The age of onset is most
often in adulthood, but renal cysts in children have been described. Metabolic
disturbances associated with kidney disease patients can also lead to chronological
enamel hypoplasia of the primary and permanent teeth (Kaya
et al., 2008), reflecting to the dysplastic changes in enamel noticed
in the female population of this report. However, the siblings in this report
were referred to a nephrologist for investigations, who confirmed no existing
The current report observes a severe expression of clinical features related to OFD1 in the 3rd generation of the family than to the earlier generations having fewer findings. Genetic counseling can provide these individuals and families with information on the nature, inheritance and implications of genetic disorders to help them make informed medical and personal decisions. The authors were successful in providing genetic counseling and helped imparting knowledge and insight regarding the familys medical condition.
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