Acro-dermato-ungual-lacrimal-tooth syndrome: case report

Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome, OMIM 103285) is a rarely seen ectodermal dysplasia disorder first described by Propping and Zerres in 1993.¹ ADULT syndrome is known as an autosomal dominant disorder. Only a family constellation^1,2 and four independent cases^3-6 were reported worldwide up to now. Here, we report a case of ADULT syndrome, which is the first case reported from China.

Clinical history
A 26-year-old woman presented to our clinic in December 2005 with complaints of right hand ectrodactyly, oligodentia and extensive freckles that have gradually developed since birth. She was born in Guangdong Province of China in 1979, with an ectrodactyly right hand. She was found to have hypodontia at the teething age, delayed eruption of the primary and permanent dentition and oligodentia. She also had epiphora and reduced sweating. More and more freckles appeared on her face after adolescent age. According to her dental records she had only the teeth in January 1999. The tooth embeddedhorizontally into the alveolar bone and the tooth had residual root. In order to accommodate a new denture, the teeth and the residual root of tooth were extracted. Trimming was made for the frenulum of upper and lower lip and hypoglossis at this time. The patient has a history of injury which resulted in phalangette excalation on her left fourth finger. She began her menarche at the age of 14 and had normal menstrual cycles. Investigation of her family history revealed that the patient's parents were not consanguineously related. No visible congenital malformation such as ectrodactyly, oligodontia, extensive freckles was observed in three generations of close relatives. The patient's sister (with same parents) and her aunt (II3) had hypoplastic breasts, but no other congenital malformation. The pedigree of the patient's family in three generations is displayed below (Fig. 1).

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Fig. 1. Pedigree of the family of the patient with ADULT syndrome. ● The patient with ADULT syndrome. ½ The patient's sister and her aunt with hypoplastic breasts.

Physical examination
The patient had normal cognitive functions. Her breasts were under-developed for her age. The right nipple was smaller than normal and the left nipple was absent (Fig. 2). Right-hand ectrodactyly was observed with absence of right middle finger (Fig. 3A). Paratelum of left ring finger was stubby. Extensive freckles, especially on her face (Fig. 4) and upper back, were seen. Scattered atrophic maculae were also present on her upper back (Fig. 5). Her scalp hair was thinner and light brown in color. The nail plates were matted. No flare around the nails and no asymphytous nail grooves were observed (Fig. 3A). Skin sweat test confirmed the diagnosis of hypoidrosis. There was no cleft lip or cleft palate. Oral examination revealed absence of majority of the teeth except for . Paramor- phia of teeth and presence of deciduous teeth are revealed (Fig. 4). Eye examination showed slight hyperemic conjunctiva and increased discharge in both eyes. Left lacrimal duct obstruction and right lacrimal duct stenosis were confirmed by lacrimal passage irrigation. Development of vulva and cervix were normal. Bimanual examination revealed a small uterus.

Laboratory examination
Blood and urine routine tests showed no abnormality. Serum chemistry profile and IgG, IgM, IgA, C3 and C4 were within normal range. The hormone level of pituitary, adrenal cortex, thyroid and gonadal gland were also within normal range. Chromosome analysis revealed a normal 46XX female karyotype.

X-ray
Frontal and lateral skull radiographs confirmed the hypo- plasia of her maxillae and mandible bones. Only three teeth in alveoli dentales of maxillae and two teeth in mandible were left in place. Bilateral antrum maxillas were smaller and hypodense (Fig. 6). Panoramic tridimen- sional image reconstruction and planar hand radiographs showed ectrodactyly at right middle finger. The third metacarpal bone was smaller significantly in size and aligned ulnad. The articular surface of distal end of the third metacarpal bone formed articulus with distal end of the fourth metacarpal bone as well as proximal phalanx of fourth finger (Fig. 3B).

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Fig. 2. Patient's breasts were under-developed. The right nipple was smaller than normal and the left nipple was absent.
Fig. 3. Ectrodactyly was seen in patient's right hand with absence of right middle finger (A). The planar hand radiographs showed ectrodactyly at the middle fingers of the right hand (B).
Fig. 4. Hypodontia with missing teeth could be seen in oral cavity and extensive freckles was remarkable on face.
Fig. 5. Scattered atrophic maculae were present on trunk.
Fig. 6. Lateral maxillae and mandiblel radiographs showed the hypoplasia of alveolar bone and absence of certain teeth.

Sonography
The colored cardiac Doppler examination showed normal size of atria and ventricles with physiological regurgitation on tricuspid valve. The abdominal sonographic image showed no abnormalities on liver, chlolecyst, pancreas, spleen, kidneys and adnexa uteri.

Skin biopsy
Skin biopsy sample was taken from a freckle on patient's back. The histopathologic findings indicated atrophy of epidermis, focal increase of melanocyte population, and collagen fibers hyperplasia in superficial layer of dermis. Eccrine gland could be identified microscopically and had a normal morphology on haematoxylin and eosin staining.

DISCUSSION

Over 170 different ectodermal dysplasias and related syndromes have been described. Many of them have overlapping clinical features.^7,8 These conditions encompass a spectrum of developmental abnormalities of skin, hair, teeth, nails and sweat glands. ADULT syndrome is a typical ectodermal dysplasias syndrome involving multiple organs. The point of gene mutation was mapped to chromosome 3q27. This is known as a missense mutant. Recently, researchers suggested that the disorder is related to the mutation in the DNA-binding domain of p63.^5,6,9

Differential diagnosis is mainly based on clinical features. Other ectodermal dysplasia syndrome such as ectrodactyly, ectodermal dysplasia, clefting syndrome (EEC), ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) and limb mammary syndrome (LMS) should be excluded before a diagnosis of ADULT can be made. ADULT syndrome can be differentiated from above diseases by the absence of facial clefts, the presence of excessive freckles and neurodermitic signs.⁹ Gene mutation sites of these syndromes are on the different region.⁵

In 1993, Propping and Zerres¹ first described the ADULT syndrome. It was characterized by ectrodactyly, extensive freckling, sparse hair and a thin skin, lacrimal duct stenosis or obstruction, nail dysplasia, hypodontia or early loss of permanent teeth, athelia or nipple and breast dysplasia, etc. Later, a case reported by Slavotinek⁶ described dysplasia such as hyphidrosis, ulnar hypoplasia with bilateral fifth finger brachydactyly, camptodactyly, as well as imperforate anus.

The case we report here has the main features of the disorder and the manifestations of ectodermal dysplasias such as ankyloglossia and atrophic maculae of skin, which is consistent with the presentations of ADULT syndrome. This disorder has been defined as an autosomal dominant inherited disease. However, only the proband among the last three generations in the pedigree has features of complete dominance of the inherited disorder. The patient's sister (with same parents) and her aunt (II3) had a phenotype of incomplete dominance. The possibility of mutant gene in patient's kindred should be further investigated.

An extensive search of literature performed by Guangdong Medical Information Institute confirmed that this case is the first report of ADULT syndrome in China. In the search process, the Chinese Bio-medicine Disc (CBM-Disc), Chinese Medical Current Contents (CMCC) and the newer print serial publication of Chinese medical journals were retrieved and reviewed.

The function of this patient's hand is compatible with the needs of daily activities. The management should focus on denture installation, dacryocystorhinostomy for lacrimal duct reconstitution, infection control of eye and genetic counseling. Freckles removal by laser and breast reconstruction can be done for cosmetic purpose. Fetal DNA detection of chorionic villi¹⁰ in the first-trimester and fetus sonography⁴ in the midtrimester help to establish an antenatal diagnosis.

REFERENCES

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2. Propping P, Friedl W, Wienker TF, Uhlhaas S, Zerres K. ADULT syndrome allelic to limb mammary syndrome (LMS)? Am J Med Genet 2000; 90: 183-184. [PubMed]

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10. South AP, Ashton GH, Willoughby C, Ellis IH, Bleck O, Hamada T, et al. EEC (Ectrodactyly, Ectodermal dysplasia, Clefting) syndrome: heterozygous mutation in the p63 gene (R279H) and DNA-based prenatal diagnosis. Br J Dermatol 2002; 146: 216-220. [PubMed]