Goltz syndrome with multiple eccrine hidrocystomas – Rare case with a novel association

INTRODUCTION

Focal dermal hypoplasia (FDH), also known as Goltz syndrome, is a rare mesoectodermal disorder inherited from an X-linked dominant gene, which is lethal in homozygous males.^[1] It was first described by Liebermann as atrophoderma linearis maculosa et papillomatosis congenitalis. Subsequently, in 1962, Goltz et al. reported three cases of FDH and distinguished them as separate entities.^[2] Over 200 cases have been reported worldwide,^[3] of which only a few are from India. We describe a rare case of Goltz syndrome along with an unusual feature of multiple eccrine hidrocystomas, which has not been reported earlier in the literature from India.

CASE REPORT

A 50-year-old female presented with complaints of multiple asymptomatic, gradually progressive, raised lesions over her face since childhood. She was born out of a non-consanguineous marriage and had multiple skeletal anomalies, facial dysmorphism, and hypopigmented skin lesions over the trunk and extremities in a generalized pattern at the time of birth. All her developmental milestones were delayed. Her mother also had hypopigmented lesions over her body and multiple raised lesions on her face in a similar pattern. Her three elder brothers died at birth.

On examination, she was mentally disabled and had short stature, facial asymmetry, with concomitant squint. She had partial anodontia, causing widely spaced dentition [Figure 1] with defective enamel development. Her fingers were short and had multiple flexion and extension deformities [Figure 2]. Her right knee had valgus deformity, and her feet showed ectrodactyly [Figure 3] and the absence of one digit. She also had scoliosis.

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Figure 1:

Abnormal dentition.

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Figure 2:

Deformed fingers with hypoplastic nails.

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Figure 3:

Feet with ectrodactyly (lobster claw deformity).

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Cutaneous examination showed multiple translucent papules and skin outgrowths of varying sizes from 0.5 × 0.5 cm to 2 × 2 cm, distributed over the face, mainly involving both cheeks, near the lateral canthus of the eyes, and the root of the nose [Figure 4]. There were multiple atrophic, depigmented, linear macules of varying sizes on the trunk and extremities, with most of them along the lines of Blaschko [Figure 5]. Nails were narrow, hypoplastic, and dystrophic [Figure 2].

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Figure 4:

Multiple hidrocystomas on the face.

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Figure 5:

Atrophic hypopigmented macules along Blaschko’s lines.

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Systemic examination was normal, but the echocardiogram showed trivial tricuspid regurgitation. Her hemogram and urine analysis were normal. An ultrasound scan of the abdomen did not reveal any abnormality.

Excision biopsy of translucent papule on histopathological examination showed vacuolar degeneration of keratinocytes with dermis showing a unilocular cystic space lined by cuboidal/flattened epithelial cells compatible with eccrine hidrocystoma [Figures 6 and 7], and skin biopsy from the atrophic macule showed dermal atrophy with thin collagen fibers consistent with FDH [Figure 8].

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Figure 6:

Cavity in dermis corresponding to eccrine hidrocystoma and vacuolar degeneration of keratinocyte denoted by red circle. (Hematoxylin and eosin stain, 4x).

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Figure 7:

Flattened epithelial cells lining the cyst cavity denoted by blue arrow. (Hematoxylin and eosin stain, 40x).

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Figure 8:

Dermal atrophy with thin collagen fibers denoted by red arrow. (Hematoxylin-eosin stain, 10x).

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DISCUSSION

FDH is an uncommon multisystem disorder. The characteristic features include Blaschko linear atrophic hypopigmented patches with telangiectasias, congenital hypo or hyperpigmentation, fat herniation through dermal defects, and multiple papillomas of the mucous membranes or skin.^[1,4] Additional cutaneous features include patchy alopecia, brittle or sparse hair, nail dystrophy or anonychia, and hyperkeratosis of the palms and soles.^[4]

Apocrine and eccrine gland anomalies and hidrocystomas have been described in Goltz syndrome.^[5] The presence of multiple hidrocystomas is also seen in another rare inherited disorder known as Schopf–Schulz–Passarge syndrome, which is an autosomal recessive form of ectodermal dysplasia characterized by hypodontia, hypoplastic nails, hypotrichosis, palmoplantar keratoderma, cysts of the eyelid margins, and multiple periocular hidrocystomas.^[6] Our patient had multiple eccrine hidrocystomas with atrophic linear depigmented macules in a blaschkoid pattern, with similar findings on her mother, and a history of death of 3 elder brothers at birth. These features are suggestive of an X-linked dominant inheritance pattern of the disease. The dental anomalies seen in FDH encompass hypodontia, oligodontia, microdontia, enamel hypoplasia, retarded eruption, lip/jaw cleft, malocclusion and rarely jaw cysts.^[1,4] Our patient had partial anodontia with defective enamel development.

Fibrovascular papillomas can involve mucosal, perigenital, intertriginous, and perioral surfaces. When found in the perianal and vulvar regions, they may be mistaken for condylomas. Less commonly, papillomas may also occur in the larynx and esophagus.^[1,4]

Ophthalmic manifestations include colobomas, strabismus, microphthalmia, and photophobia.^[6] Of these, our patient has strabismus.

Skeletal anomalies are frequent and often present asymmetrically. Our patient had ectrodactyly, scoliosis, genu valgum, missing digits, and short digits, consistent with the reported literature.^[1,4] Other reported features include polydactyly, hypoplasia of digits, clavicular dysplasia, and spina bifida occulta. The characteristic radiological change is osteopathia striata of the long bones.^[1]

Other occasional anomalies include short stature, joint hypermobility, mental retardation (15%), hearing defects, microcephaly, structural abnormalities of the kidney like horse-shoe kidneys, umbilical, inguinal, epigastric, or diaphragmatic hernias. Cardiac anomalies include cardiac tumors and congenital heart diseases like truncus arteriosus.^[1,4] Of these, our patient had short stature, hearing defects, and intellectual disability.

Although the patient declined genetic testing due to financial limitations, a diagnosis of Goltz-Gorlin syndrome was made based on the presence of multiple characteristic features of FDH. The additional features present in this case were multiple eccrine hidrocystomas and trivial tricuspid regurgitation.

Treatment of FDH is largely supportive. As it is a multisystem disease, a multidisciplinary approach is required for the effective management of these patients. Multiple hidrocystomas are challenging to treat because of their multiplicity and cosmetic location. Treatment options include topical anticholinergic agents such as atropine, lesional drainage, lasers, and surgical excision.^[7] Due to financial limitations, advanced therapeutic interventions were not feasible for the patient. Accordingly, detailed counseling was provided regarding the disease prognosis and the spectrum of available treatment options, enabling informed decision-making within the context of resource constraints. They opted for surgical excision of a few hidrocystomas and were subsequently referred to the orthopaedics department for comprehensive management of the associated skeletal anomalies.

CONCLUSION

FDH with multiple eccrine hidrocystomas is a rare association that prompted us to report this case.