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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.78 no.1 Rio de Janeiro Jan./Feb. 2003
Goltz syndrome: report of two cases*
Ilner de Souza-e-SouzaI; Paula Cristina Assef dos Santos CunhaII
degree in dermatology, Medical Doctor at the Fundação Alfredo da Matta - Manaus
- Amazonas, professor of dermatology at the Fundação Universidade do Amazonas
IIMedicine student, Fundação Universidade do Amazonas
Focal dermal hypoplasia is a rare X-linked dominant genodermatosis. Two cases of Goltz-Gorlin syndrome are reported, showing the clinical manifestations, necessity of multidisciplinary evaluation, diagnosis and continuous follow-up.
Key words: atrophy; focal dermal hypoplasia.
Focal dermal hypoplasia was first described by Lieberman in 1935.1 Cole et al.2 reported a mesoderm and ectoderm dysplasia with bone alterations, probably corresponding to the second publication of this entity. Goltz et al.3 (1962) and Gorlin et al.4 (1963) delineated the main characteristics of this nosologic entity and defined its nomenclature.
It is a rare genodermatosis with approximately 200 published cases, which involves multiple organs besides the skin.1,5 The main cutaneous characteristics of the lesions are: atrophic; hyper-, hypo- or achromic; xanthomatous; present at birth; following the lines of Blaschko; and in some cases can have a reticular disposition.6
The presence of vegetative fibrovascular periorificial lesions - oral, perineal, vulvar - can cause them to be confused with condyloma acuminatum or vulgar warts. However, they are not associated with human papilloma virus (HPV).7
The main annexal alterations described are: scant and fragile hair; anomalies of the apocrine glands; and unguinal deformities, such as atrophy, dystrophy, concavity, grooves and even anonychia.7,8
Sometimes, the oral cavity is involved, with alterations in the number, size and structure of the teeth. Hypodontia, microdontia, hypoplasia of the enamel and retarded dental eruption can occur.9
Bone involvement is frequent. The presence of longitudinal striations - grooved osteopathy - crossing the metaphyses of the long bones is the most characteristic finding, although it is not always present. The important characteristics are: absence or hypoplasia of the digits, syndactylia, lobster-claw deformities in the hands and feet, corporal asymmetry, scoliosis and spina bifida.5,8
Most of the cases occur in the female sex and it is characterized by being a pathology with dominant inheritance linked to chromosome X. It is generally lethal to male fetuses. The rare occurrence of cases in men can represent post-zygotic mutation that would from then on be transmitted to the individual's descendents, with exclusive clinical expression in the female sex.9
Ultra-structural studies of cutaneous lesions have demonstrated a significant increase of collagen type III in the dermis and absence of collagen type IV in the basal membrane area.6
The main histopathological characteristics of the cutaneous lesions are: dermal atrophy, edema present in the papillary dermis as well as mononuclear infiltration and fibrosis in the area of the dermis permeated by fatty tissue.10 The diverse alterations observed can vary according to each individual and the lesion in which the biopsy is performed.
MCR, female, white, seven years old, natural of Manaus. From birth she presented hypochromic and atrophic lesions with a cribriform or reticular distribution in the face, cervical area (Figure 1), inguinal, gluteal and posterior surface of the inferior members. These were predominantly in the right half of the body. Interspersed among the lesions of the thighs were yellowish, papular, lesions, corresponding to fatty herniation. Telangiectasia could be observed with lineal disposition in the cervical, inguinal and right gluteal areas.
Presence of agenesis in the fourth right toe, implantation anomaly in the thumbs, lobster-claw deformity in the right foot and cifoscoliosis was verified (Figure 2). X-ray exam of the column revealed butterfly vertebra in the 6th thoracic.
Vascular and neurological anomalies were not observed. Ophthalmologic exam only detected simple myopic astigmatism.
Ultrasound scan of pelvic and abdominal organs, complete blood count, urinalysis, parasitology of feces, tests of renal and hepatic function, ionogram, erythrocyte sedimentation rate (ESR), iron count, lipidogram and total proteins were all normal.
Histopathological exam revealed dermal atrophy, rarefaction of the collagenous fibers, reduction of the annexes and herniation of the fatty tissue within the atrophic dermis.
The patient was submitted to amputation of the fourth right toe, in order to improve her adaptation to shoes.
JFC, female, white, nine years old, natural of Manaus. Sought the medical service due to the presence of vesicles and festering ulceration in the inferior members.
From birth she presented atrophic lesions, some of which were hypochromic and others hyperchromic and erythematous with a predominantly linear disposition and some in reticular arrangements. They involved the right thoracic, left abdominal and gluteal regions, right arm and inferior members, reaching the feet. Fatty herniation was observed in the region of these lesions, as well as low implantation of the ears.
The cutaneous atrophy of the lesions enabled the blood vessels of the inferior members to be clearly seen, which could be interpreted erroneously as varicose veins or manifestation of Pick-Herxheimer disease.
Furthermore, characteristic lobster-claw deformity was observed in the feet, cubital deviation in the interphalangeal joints of the hand and cifoscoliosis.
Skull x-ray revealed persistence of the left parietal foramen. Ophthalmologic exam presented microphthalmia (Figure 3) and amaurosis in the right eye. The left eye, however, was normal.
Other findings were microencephaly, hypertrophy of the tonsils, unguinal dystrophy, microdontia, low implantation of the ears and difficulty in elocution. The patient presented recurrent infection of the tonsils.
No anomalies were observed in the cardiovascular and respiratory systems.
Anatomicopathological study revealed normal epidermis, atrophic dermis with shortage of collagen fibers and permeated by fatty tissue.
Ultrasonography of the pelvic and abdominal organs right kidney showed normal form and volume, however with medial rotation and discreet pelvic dilation. The other organs were morphologically normal.
Leukokinetics, urinalysis, parasitology of feces, tests of renal and hepatic function, ionogram (sodium, potassium, chloride and phosphate), ESR, iron levels (serum iron, ferritin and transferrin), lipidogram and total proteins were normal. She presented anemia (hematocrit 35%, and hemoglobin 11.2mg%).
Goltz syndrome is a rare genodermatosis, demonstrated by alterations of several tissues and/or organs. (Chart 1) Faced with these characteristics, the denomination of focal dermal hypoplasia is somewhat simplistic.
In most of the cases described in the literature, the cutaneous alterations are predominantly unilateral, which was confirmed in the first case presented here. However, in the second case the cutaneous lesions were bilateral.
For the dermatologist, the diagnosis of Goltz syndrome is essentially clinical. The main alterations observed in the skin are hyper-, hypo- and/or achromic atrophic lesions, which can sometimes be erythematous, dispersed lineally, in a reticular pattern, as well as with yellowish papular, hernial lesions, corresponding to the projection of fatty tissue into the atrophic dermis.6 All these findings were present in the patients of this report.
There are descriptions of areas of cutaneous aplasia demonstrated by cutaneous ulcer present at birth and that courses to atrophic scarring.6 Xerosis, telangiectasia, photosensitivity, lipomatous hamartoma and pruritus in the atrophic areas have also been described.11 However, these characteristics were not observed in the present cases.
Other important alterations that can be verified using ectoscopy are lobster-claw deformities in the hands and feet, as well as cifoscoliosis. The importance of recognizing these deformities should be kept in mind in order to establish a diagnosis of Goltz syndrome.
In the first case study, corrective orthopedic surgery of the right foot was performed, which facilitated the patient's social conviviality and enabled her to use closed shoes, which are obligatory in the state schools.
The occurrence of osteopathia striata was not verified in the described cases, even though this is a frequent and characteristic finding in Goltz syndrome. Nevertheless, its presence can occur separately (Voorhoeve's disease) or in combination with other forms of bone condensation, such as osteopoikilosis or other poorly defined conditions with partial osteosclerosis.12,13,14
Besides the alterations observed in Case 2 - amaurosis and microphthalmia - anophthalmia, coloboma, squint, nystagmus, and cysts of the tear ducts, as well as alterations of the cornea, for instance, subcapsular and cortical cataract, microcornea and keratoconus have been described previously.9
Other systemic manifestations can be observed: agenesis or renal coalition; horseshoe kidney; omphalocele; agenesis of the callous body; hydrocephalus; myelomeningocele; persistence of the thyroglossal duct; cardiovascular and lung alterations; as well as malformations in the digestive tract and diaphragm. Varied degrees of mental retardation have also been reported.15
Wechler et al.16 have postulated that the varying degrees of involvement in this entity can be explained by the more precocious or tardive inactivation of the gene responsible for the syndrome. The reported cases clearly demonstrate the diversity of these forms of presentation.
Despite the differences in the presentation of the syndrome between the two cases described here, their diagnoses were confirmed by histopathological exam, in that atrophic dermis was found, with significant alteration of collagen, rarefaction of annexes and herniation of fatty tissue amidst the atrophic dermis.
Since this is a genetically inherited entity, genetic counseling is necessary to advise patients with this syndrome that they should avoid having children as there is a high risk that their descendents will also present the syndrome.
The importance of a multidisciplinary attendance for these cases is underscored, with a view to diagnosing, following up and treating the impairment of all affected organs or systems, thereby offering better life quality to the patients.
Finally, a possible confusion should also be highlighted that can occur while consulting the literature, due to the similarity between the eponyms Goltz-Gorlin, whose syndrome was studied here and Gorlin-Goltz, represented by basal cell nevus syndrome.17
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Ilner de Souza e Souza
Rua Acre nº 12 CEMOM sala 617
Manaus AM 69065-100
Tel/Fax: (92)232-0286 / 232-4257
Received in February, 6th of 2001.
Approved by the Consultive Council and accepted for publication in August, 07th of 2002.
* Work done at Dermatology Service of "Fundação Alfredo da Matta" and "Ambulatório Araújo Lima da Fundação Universidade do Amazonas - FUA".