Printer Friendly

Case report: presentation of lacrimo-auriculodento-digital (LADD) syndrome in a young female patient.


Lacrimo-auriculo-dento-digital (LADD) syndrome (OMIM #149730) is a very rare autosomal-dominant congenital multiple anomaly disorder characterized by aplasia (developmental absence of all or part of an organ), atresia (closure or blockage of a body passage), or hypoplasia (underdevelopment or incomplete development) of the lacrimal and salivary systems, cup-shaped ears, hearing loss, and dental anomalies [Milunsky et al., 2006]. Furthermore, variable anomalies of the hands and feet, such as duplicated terminal phalanx of the thumb, triphalangeal thumb (long finger-like thumb with three phalanges instead of two), preaxial polydactyly (thumb duplication), syndactyly (fusion) of the second and third digits, and fifth finger clinodactyly (curving of the fifth finger towards the fourth) have also be seen in cases with LADD [Guven et al., 2008]. Additional features of the syndrome may include renal abnormalities such as agenesis (failure of an organ to develop during embryonic growth) or nephrosclerosis (sclerosis of the kidney), hiatus hernia (protrusion of the upper part of the stomach into the thorax through a tear or weakness in the diaphragm), and coronal hypospadias (ventral and proximal malposition of meatus in the coronal sulcus) [Jones and Smith, 2005; Bamforth and Kaurah, 1992]. Intracranial manifestations, such as calcifications of the basal ganglia have also been reported in patients with LADD syndrome [Haktanir et al, 2005].

The degree to which the different organs are involved varies considerably with dental anomalies regularly reported. Such abnormalities may include peg-shaped incisors, long thin-rooted teeth, malformed molars, microdontia, enamel hypoplasia, shallow cusps, taurodontism and partial anodontia [Levy, 1967]. This report details the first reported presentation of LADD syndrome in the Republic of Ireland with a 12-year-old girl who exhibited a range of dental and digital abnormalities.

Within the medical literature there are less than 50 reported cases of LADD syndrome, also known as the Levy-Hollister syndrome. In 1967 Levy first reported on a 'new combination of anomalies'. He described a patient with aplasia of the nasolacrimal duct, malformation of the auricles, a dry mouth, pronounced dental anomalies (unerupted and dysplastic teeth), and digital anomalies [Levy, 1967]. Hollister et al. [1973] independently described a family with similar symptoms and signs of an autosomal-dominant transmission. It was this workgroup that coined the term lacrimo-auriculodento-digital (LADD) syndrome.

In addition to the clinical signs initially observed by Levy and by Hollister et al., other authors assigned further clinical findings to this syndrome (Table 1). These included varyingly expressed dysplasia of the auditory apparatus (e.g. auricular dysplasia, congenital hearing loss), renal abnormalities, e.g. agenesis or nephrosclerosis, hiatus hernia, facial dysmorphia, and epiglottic hypoplasia. A number of reports have detailed anomalies of the hands and feet, such as duplicated terminal phalanx of the thumb, triphalangeal thumb, preaxial polydactyly, syndactyly of the second and third digits, and fifth finger clinodactyly [Poznanski et al., 1972; Murdoch-Kinch and Miles, 1996].

Mixed sensorineural and conductive hearing loss, either unilateral or bilateral, is frequently found in patients with LADD syndrome. Although this hearing loss is usually mild to moderate, severe hearing loss has been reported. Improvements in hearing loss have been detailed after surgical intervention for middle ear abnormalities. Although the hearing loss at birth may be profound there can be a progressive component with reduced auditory acuity being detected for the first time in adults. Performing periodic hearing tests on all persons with LADD syndrome has been recommended [Wiedemann and Drescher 1986].

Reported lacrimal apparatus malformations have included nasolacrimal duct obstruction and hypoplasia or aplasia of the lacrimal puncta. It has been suggested that the basis for the decreased lacrimation in patients with LADD syndrome may be acinar aplasia or hypoplasia. It is thought that the basal secretion from the accessory lacrimal glands may provide sufficient tears to maintain the integrity of the corneal epithelium [Inan et al., 2006]. Another reported feature of this syndrome is congenital ptosis that in some cases may be associated with hypertelorism and telecanthus [Bamforth and Kaurah, 1992].

Salivary gland pathologies are commonly reported with LADD syndrome. Congenital absence of the major salivary glands has been described and affected patients may suffer from xerostomia. Even in the presence of submandibular and parotid glands with patent ductal systems, markedly reduced secretions have been found in some patients. Shiang and Holmes [1977] described absence of the parotid glands and Stensen's ducts in one of two patients with the Levy-Hollister syndrome. However, Kreutz and Hoyme [1988] surmised that the defects of salivary glands might not represent an associated feature of LADD syndrome because of absence of this defect in other affected individuals. The congenital absence of major salivary glands resulting in xerostomia has been reported without evidence of the LADD syndrome [Smith and Smith, 1977; Whyte and Hayward, 1989].

Another syndrome named the branchio-otorenal (BOR) syndrome may share a number of features of LADD syndrome and may necessitate differential diagnosis with LADD syndrome. The BOR syndrome can be distinguished from LADD syndrome by the presence of auricular pits and branchial fistulae and absence of dental and digital anomalies.

Ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome is distinguished by the presence of split hand/foot, by hair and skin anomalies and by cleft lip with or without cleft palate. Propping and Zerres [1993] reported a family with close resemblance to the LADD and EEC syndromes and related disorders. The main manifestations were hypodontia and/ or early loss of permanent teeth, ectrodactyly, obstruction of lacrimal ducts, onychodysplasia, and excessive freckling. They proposed the acronym ADULT (acro-dermato-ungual-lacrimal-tooth)-syndrome for this condition.

Previously pathogenetically unclarified, the genetic cause of LADD syndrome has been identified as heterozygous mutations in the encoding of fibroblast growth factor receptors FGFR2 and FGFR3. It has also been found that LADD is associated with the mutations in the FGF10 gene, which has been shown to result in agenesis of the lacrimal and salivary glands [Milunsky et al, 2006; Shams et al., 2007; De Coster et al., 2009].

Case Report

The Community Dental Service referred a 12-year-old girl to Cork University Dental Hospital. The patient was born in the Republic of Ireland to Moldovan parents. She had previously been diagnosed with LADD syndrome in a regional hospital within Ireland. The patient was under the medical care of her family medical practitioner who revealed that genetic testing in combination with clinical signs had been used to give a diagnosis of LADD. Questioning of the patient and her mother revealed no known previous family history of LADD syndrome and her younger siblings were unaffected. Genetic counselling had not been carried out for family members.

The patient's primary dental complaint was the appearance of her maxillary anterior teeth that she felt were small and spaced. The patient was taking no medications, had no known allergies and was otherwise medically well. No history of neonatal or perinatal complications was noted. The patient gave no history of renal symptoms or involvement of other major organs.


Extra oral examination. This revealed a prominent chin with a notable deviation to the right. The patient had cup shaped ears and mild ptosis but no further otolaryngologic abnormalities. The patient exhibited no evidence of deafness or hearing loss and reported no dryness of her eyes. (Figure 1)

Intra-oral examination: There was a mixed dentition with evidence of previous caries and untreated lesions present. Despite the evidence of caries there was no evidence of hypoplasia or other anomalies of the dental hard tissues. There was little clinical evidence of xerostomia and a normal salivary flow test was recorded, however the patient's mother reported she frequently sipped bottled water. The maxillary and mandibular permanent incisors were present and clearly spaced (Figure 2). The maxillary central incisors, particularly 11, were diminutive and an orthopantomogram revealed that 25, 35 and 45 were absent (Figure 3) in addition to all second permanent molars (17, 27, 37 and 47).




An examination of the patient's feet revealed no obvious abnormalities but her hands exhibited a number of anomalies (Figure 4). On her right hand there was evidence of fifth finger clinodactyly and preaxial polydactyly of the thumb. Her left hand also exhibited fifth finger clinodactyly and a triphalangeal thumb. The patient reported no functional difficulties with her hands but found gripping objects difficult with her left hand.


The dental treatment for this patient necessitated a multidisciplinary approach encompassing restorative and orthodontic elements. The initial treatment strategy involved preventative elements including fissure sealing unrestored first permanent molars, extensive oral hygiene instruction and the use a high fluoride mouthwash and dentifrice. Teeth with cavities present were restored.

As an interim measure, impressions of the patient's dentition were taken and a diagnostic wax up completed to illustrate the improvements that could be made to the shape of the anterior teeth. Wax was added to increase the width of the incisors and canines but not the length of the teeth, in order to maintain the existing occlusion. After a discussion with the patient, a number of minor adjustments were made to the contour of the teeth on the wax up. The exact shape of the teeth achieved with the diagnostic wax up was transferred to the teeth in the mouth after fabrication of maxillary and mandibular putty matrices. Composite resin was applied to the maxillary and mandibular incisors and canines to provide definite restorations (Figure 5).



The patient has been reviewed after provision of her composite build-ups. The resin composite was polished and a small repair made to the palatal surface of the right maxillary lateral incisor. The patient was very pleased with the outcome of the restorative treatment and she is now maintaining a good standard of oral hygiene.

The patient now requires orthodontic treatment that will be designed to provide appropriately sized spaces for the missing premolars which can then be restored with fixed prostheses. The composite resin restorations on the anterior teeth will be maintained until gingival maturity is reached, when extra coronal restorations could be considered. Her medical management will continue to be managed by her family practitioner.


Lacrimo-auriculo-dento-digital (LADD) syndrome is an autosomal-dominant congenital multiple anomaly disorder. There are less than 50 reported cases of LADD syndrome in the medical literature with a variety of manifestations reported. This report details the presentation of a young girl with a sporadic case of LADD syndrome who presented with notable dental and digital abnormalities. The condition had not affected her auditory, lacrymal or renal systems as in other reported cases but this serves to illustrate the variable systemic expression of LADD syndrome.


Bamforth JS, Kaurah P. Lacrimo-auricular-dento-digital syndrome. Evidence of lower limb involvement and severe congenital renal abnormalities. Am J Med Genet 1992; 43: 932-37.

Calabro A, Lungarotti MS, Mastroiacovo P. Lacrimo-auriculo-dento-digital (LADD) syndrome. Eur J Pediatr 1987; 146: 536-7.

De Coster PJ, Marks LA, Martens LC, Huysseume A. Dental agenesis: genetic and clinical perspectives. J Oral Pathol Med 2009; 38: 1-17.

Francannet C, Vanlieferinghen P, Dechelotte, Urbain MF et al. LADD syndrome in five members of a three-generation family and prenatal diagnosis. Genet Couns 1994; 5: 85-91.

Guven Y, Rosti RO, Tuna EB, Kayserili H, Aktoren O. Orodental findings of a family with lacrimo-auricular-dento-digital (LADD) syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 106: e33-e44.

Haktanir A, Degirmenci B, Acar M, Albayrak R, Yucel A. CT findings of head and neck anomalies in lacrimo-auricular-dento-digital (LADD) syndrome. Dentomaxillofac Radiol 2005; 34: 102-5.

Heinz GW, Batemann JB, Barret DJ, Thangavel M, Crandall BF. Ocular manifestations of the lacrimo-auriculo-dento-digital syndrome. Am J Ophthalmol 1993; 115: 243-8.

Hennekam RC. LADD syndrome: a distinct entity? Eur J Pediatr 1987; 146: 94-5.

Hollister DW, Klein SH, De Jager HJ, Lachman RS, Rimoin DL. The lacrimo-auricular-dento-digital syndrome. J Pediatr 1973; 83: 438-44.

Horn D, Witkowski R. Phenotype and counselling in lacrimo-auriculo-dento-digital (LADD) syndrome. Genet Couns 1993; 4: 305-9.

Inan UU, Yilmaz MD, Demir Y, et al. Characteristics of lacrimo-auriculo-dento-digital (LADD) syndrome: Case report of a family and literature review. Int J Pediatr Otorhinolaryngol 2006; 70: 1307-14.

Jones KL, Smith DW. Smith's unrecognisable patterns of human malformation. 5th ed. Philadelphia. W B Saunders Co; 2005 p. 360-61.

Kreutz JM, Hoyme HE. Levy-Hollister syndrome. Pediatrics 1988; 82: 96-9

Lehotay M, Kunkel M, Wehrbein H. Lacrimo-auriculo-dento-digital syndrome. Case report, review of the literature and clinical spectrum. J Orofac Or thop 2004; 65: 425-32

Levy WJ. Mesoectodermal dysplasia: a new combination of anomalies. Am J Ophthalmol. 1967; 63: 978-82.

Meuschel-Wehner S, Klingebiel R, Werbs M. Inner ear dysplasia in sporadic lacrimo-auricular-dento-digital syndrome. A case report and review of the literature. ORL J Otorhinolarngol Relat Spec 2002; 64: 352-4.

Milunsky JM, Zhao G, Maher TA, Colby R, Everman DB. LADD syndrome is caused by FGF10 mutations. Clin Genet 2006; 69: 349-54.

Murdoch-Kinch CA, Miles DA. Clinical and radiographic features of the lacrimo-auriculo-dento-digital syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996; 81: 727-35.

Poznanski AK, Garn SM, Nagy JM, Gall JC. Metacarpophalangeal pattern profiles in the evaluation of skeletal malformations. Radiology 1972; 104:1-11.

Propping P, Zerres K. ADULT-syndrome: an autosomal-dominant disorder with anomalies, ectrodactyly, nail dysplasia and hypodontia. Amer S Med Genetics 1993;45:642-48.

Roodhooft AM, Brussaard CC, Elst E, van Acker KJ. Lacrimo-auriculo-dento-digital (LADD) syndrome with renal and foot anomalies. Clin Genet 1990; 38: 228-32.

Shams I, Rohmann E, Eswarakumar VP, et al. Lacrimo-Auriculo-Dento-Digital Syndrome Is Caused by Reduced Activity of the Fibroblast Growth Factor 10 (FGF10)-FGF Receptor 2 Signaling Pathway. Mol Cell Biol 2007; 27: 6903-12

Shiang EL, Holmes LB. The lacrimo-auriculo-dento-digital syndrome. Pediatrics 1977, 59: 927-30.

Smith NJ, Smith PB. Congenital absence of major salivary glands. Br Dent J 1977; 142: 259-60.

Thompson E, Pembury M, Graham JM. Phenotypic variations in LADD syndrome. J Med Genet 1985; 22: 382-5.

Toumba KJ, Gutteridge DL. Lacrimo-auriculo-dento-digital syndrome: a literature review and case reports. Quintessence Int 1995; 26: 829-39.

Wiedemann HR, Drescher J. LADD syndrome: Report of new cases and review of the clinical spectrum. Eur J Pediatr 1986; 144: 579-82.

Whyte AM, Hayward MW. Agenesis of salivary glands: a report of two cases. Br J Radiol 1989: 62: 1023-26.

G. J. McKenna, F. M. Burke, K Mellan.

Dept of Restorative Dentistry, School of Dentistry, University College Cork, Cork, Ireland.

Postal address: Dr G. J. McKenna, Dept. Restorative Dentistry, School of Dentistry, University College Cork, Cork, Ireland.

Table 1. Reported manifestations of oral and other anomalies
for subjects with LADD syndrome.

Manifestations        Reported Cases

Peg shaped incisors   Shiang and Holmes, [1977]; Thompson et al,
                      [1985]; Hennekam, [1987]; Calabro et al.,
                      [1987]; Kreutz and Hoyme, [1988]; Bamforth and
                      Kaurah, [1992]; Heinz et al., [1993]; Francannet
                      et al., [1994]; Toumba and Gutteridge, [1995];
                      Murdoch-Kinch and Miles, 1996.

Hypodontia            Levy, [1967]; Thompson et al, [1985]; Hennekam,
                      [1987]; Bamforth and Kaurah, [1992]; Toumba and
                      Gutteridge, [1995] Murdoch-Kinch and Miles,
                      [1996]; Meuschel-Wehner et al, [2002]; Lehotay
                      et al, [2004]; Hak-tanir et al, [2005]; Inan et
                      al, [2006].

Enamel hypoplasia     Hollister et. al., [1973] ; Horn and Witkowski,

Unerupted teeth       Levy, [1967].

Molars with single    Toumba and Gutteridge,[1995]; Lehotay et al.,
conical roots         [2004]; Guven et al, [2008].

Taurodontism          Guven et al., [2008].

Root dilacerations    Lehotay et al., [2004]; Guven et al., [2008].

Skeletal Class III    Wiedemann and Drescher, [1986]; Kreutz and
                      Hoyme, [1988]; Toumba and Gutteridge,[1995];
                      Lehotay et al., [2004]; Guven et al., [2008].

Salivary gland        Levy, [1967]; Roodhooft et al., [1990]; Shiang
abnormalities,        and Holmes, [1977]; Thompson et al., [1985];
xerostomia            Wiedemann and Drescher, [1986].

Auricular anomalies   Hollister et al., [1973]; Levy, [1967]; Thompson
                      et al., [1985].

Lacrimal anomalies    Hollister et al., [1973]; Levy, [1967]; Shiang
                      and Holmes, [1977]; Thompson et al., [1985];
                      Wie-demann and Drescher [1986].

Digital anomalies     Bamforth and Kaurah, [1992]; Heinz at al.,
                      [1993]; Hollister et al., [1973] ; Levy, [1967]
                      ; Thompson et al., [1985] ; Wiedemann and
                      Drescher, [1986].

Renal abnormalities   Roodhooft et al., [1990]; Shiang and Holmes,

COPYRIGHT 2009 European Academy of Paediatric Dentistry
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2009 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:McKenna, G.J.; Burke, F.M.; Mellan, K.
Publication:European Archives of Paediatric Dentistry
Article Type:Report
Geographic Code:4EUIR
Date:Dec 1, 2009
Previous Article:Case report: report of a rare case of juvenile recurrent parotitis and review of literature.
Next Article:Short communication: graph for calculating maximum local analgesic dose in millilitres for the paediatric population.

Terms of use | Copyright © 2017 Farlex, Inc. | Feedback | For webmasters