Mal de Meleda with Congenital Cataract: A Novel Case Report.

Mal de meleda (MdM), a rare autosomal recessive genodermatosis is characterized by erythema and hyperkeratosis of the palms and soles with a sharp demarcation and that progress with age (progrediens) and extend to the dorsal aspects of the hands and feet (transgrediens). It has been associated with various conditions albeit rarely with congenial cataract. Ocular lens and the skin have the same embryological origins. We hereby present this novel case report of Mal de meleda in association with congenital posterior subcapsular cataract which to the best of our knowledge has not been reported from India before.

What was known?

Palmoplantar keratodermas are rare genodermatosis.

Mal de Meleda is associated with varied manifestations.

Ocular lens and skin have the same embryological origins.

Introduction

Keratosis palmoplantaris transgrediens of Siemens or Mal de Meleda (MdM) is a rare autosomal recessive genodermatosis with a prevalence of one in one lakh.[1] It is named after the Dalmatian island of Meleda where its relative frequency is due to inbreeding.[2] The keratoderma usually begins between 0 and 3 years of age and is characterized by progressive “transgradiens” i.e., extension on the dorsal surface of hands and feet, hyperkeratotic plaques on the dorsum of the hands, feet, knee elbows, medial malleoli, perioral erythema, hyperhidrosis and nail changes.[2]

Although MdM has been associated with varied nail, lip and perioral changes, ocular associations have been rarely described in the English literature, which were found in our present case.

Case Report

A 10-year-old female born of consanguineous marriage [Figure 1] presented to the dermatological consult for gradually increasing thickening of palms and soles since infancy and progressing to involve dorsal aspect of hands and feet associated with hyperhidrosis. There was history of posterior subcapsular cataract extraction with an intraocular lens placement in the left eye at the age of 3 months. There was family history of palmoplantar keratoderma in paternal grandmother and congenital cataract in one of the cousins. She had two siblings aged 12-year female and 14-year male, who had no similar complaints [Figure 2a].

Figure 1

The pedigree chart with arrow depicting affected individuals

Figure 2

(a) Hands of patient and siblings. (b) Showing hyperkeratotic lesions on knee

On examination, palms and soles showed diffuse erythema and palmoplantar keratoderma extending on the dorsal surface of hands and feet with sharp margins [Figures 3a and b]. Irregular erythematous hyperkeratotic papules were present on bilateral knees [Figure 2b]. Teeth and hair showed no abnormality. General physical examination was unremarkable except that she was left handed. The left eye showed pseudophakia. The right eye was normal. Laboratory investigations including complete blood counts were within normal limits. A skin biopsy from the right palmar margin was preformed which showed hyperkeratosis, parakeratosis, psorasiform acanthosis and mild perivascular chronic inflammatory infiltrate. She was treated with oral vitamin. A 50,000 IU/day for 15 days and topical salicylic acid and urea, to which she responded well as the erythema and hyperkeratosis of the lesions decreased [Figure 4].

Figure 3

Diffuse erythema and palmoplantar keratoderma extending on the dorsal surface of hands and feet with sharp margins

Figure 4

Pre and post treatment (decreased erythema and hyperkeratosis) palmar lesions

Discussion

The nosology of palmoplantar keratodermas (PPKs) is complex. They can be both autosomal dominant and recessive [Table 1].[34] There is a great interindividual variation in the clinical manifestations of MdM which should be differentiated from other similar syndromes. Autosomal recessive PPK's which should be differentiated are Olmsted syndrome which is a cicatrizing syndrome with involvement of hair, nail and mucosa. Papillon Lefevre syndrome is characterized by palmoplantar hyperkeratosis, severe periodontitis and premature loss of teeth.[34] MdM should be differentiated from other autosomal dominant types like Thost Unna PPK by the absence of transgradiens; Greither's disease which spares the palms and soles and tends to improve with age; Huriez syndrome which is a triad of congenital scleroatrophy of distal extremities, lamellar keratoderma and nail changes; Vohwinkel's syndrome by characteristic honeycomb-like keratoderma, stellate keratoses, sensorineural deafness.[34] Our patient fitted into the diagnosis of MdM. The obligatory and facultative clinical features of MdM are discussed in Table 2.[5]

Table 1

The different patterns of inherited palmoplantar keratodermas

Table 2

Obligatory and facultative features of Mal de Meleda type of PPK

MdM may be associated with hyperkeratotic plaques on the dorsa of hands, feet, knees, elbows and medial malleoli, erythema of palms and soles, perioral eczema, hyperhidrosis. Fingers may be short and nails may show koilonychia or subungual hyperkeratosis. Other rare features include lingua plicata, syndactyly, high arched palate, left handedness, hair on the palms and soles.[6]

Ocular associations of MdM have been described by Durmus et al., in a case presenting with bilateral macular deposits.[7]

Congenital cataract is a major eye abnormality often leading to blindness. Non-syndromic familial cataracts are usually inherited as a dominant trait, while the autosomal recessive and X-linked forms are less common. There are only two reports of congenital cataract and MdM in a consanguineous Tunisian family.[8] Genetic studies have reported splice variation (c. 1327 + 4A-G) in the HSF4 gene in autosomal recessive congential cataracts. But how far are they involved in MdM associated with congenital cataracts needs deeper understanding at the genetic level and further genetic analyses to confirm or exclude the involvement of the HSF4 gene or one of the loci.[910]

While there have been few case reports of MdM from India, associations, e.g. perioral erythema,[11] hyperkeratotic knuckle pads,[1011] have been reported sparsely. To the best of our knowledge, the coexistence of both MdM and congenital cataract in the same patient of Indian origin has not been reported previously. The two phenotypes might segregate separately, although their co-occurrence could be more than a coincidental finding as the lens and the skin have the same embryological origins.

What is new?

Ocular manifestations have been sparsely reported with MdM

Congenital cataract may be associated with MdM by the virtue of the HSF4 gene involvement.