Type VIII - Ehlers Danlos Syndrome with café-au-lait macules: A Rare Variant.

Sir,

A 22-year-old, male patient born out of non consanguineous marriage presented with complaints of easily stretchable and very soft skin since birth along with poor wound healing. He complained of continuous dull aching pain involving the hip joint and the knee joints and recurrent attacks of migraine but did not experience joint popping or bruising of skin. He had normal vision and was doing well academically. He had no other systemic complaints. His mother had similar soft and stretchable skin, but in the absence of other associated complaints.

He was 159 cm tall with an arm span of 162 cm. He had low set ears, low set hairline, high arched narrow palate, and flat/rocker bottom foot. Small joints of hands were hyper extensible- Biegton's sign being positive [Figure 1] (able to touch the tip of thumb to flexor aspect of forearm easily). Swan neck deformity was seen in a few fingers. Patient's skin was very soft, thin, and hyper extensible, especially over extremities and face which was recoiling back to normal immediately [Figure 2]. Multiple well-defined, oval to round, discrete, brownish macules ranging from 1 to 5 mm were distributed over neck and trunk (suggestive of Café –au-lait macules) [Figures 3 and 4]. A few hyper pigmented and blackish macules and plaques were present over anterior and lateral aspect of the bilateral lower leg (suggestive of pretibial plaques of EDS). Few atrophic scars were present on the forehead and knees.

Figure 1

Biegton's sign- Hyper extensible Small joints of hand

Figure 2

Easily stretchable soft velvety skin

Figure 3

Café –au-lait macules on the face and neck

Figure 4

Cafe-au lait macules on the trunk

Complete hemogram, bleeding time, clotting time, and chest X-ray were within normal limits. 2D–Echo showed accessory valves near mitral valve. Dental examination revealed periodontitis in relation to lower anterior incisors [Figure 5]. On ocular evaluation, fundus showed deep Cup with Cup–Disc Ratio 0.7. There was no lens subluxation. Special stain - Verhoeff Van Gieson's on biopsy specimen of soft stretchable skin showed sparse and broken collagen bundles [Figure 6a]. Histopathology of café –au-lait macule showed increased melanin in the basal layer with macromelanosomes confined to dermo-epidermal junction, without cellular atypia [Figure 6b].

Figure 5

Periodontitis in relation to lower anterior incisors

Figure 6

(a) Broken collagen fibers are stained bright red with Verhoeffs van Gieson stain (×40) (b) Basal hyperpigmentation and macromelanosomes of epidermis, no deeper pigmentation and cell atypia (H and E stain, ×40)

The main feature that discriminates EDS-VIII from other forms of EDS is severe early-onset periodontitis. Periodontitis is characterized by irreversible destruction of the periodontal tissues like periodontal ligament, alveolar bone, and connective tissue. It manifests as premature periodontal inflammation and gingival recession, usually detectable in childhood, with rapid progression throughout adolescence and early adulthood and later complete loss of dentition.[123] Circumscribed hemosiderotic pretibial plaques, which could be thickened or atrophic, were noted in many of these patients. Affected individuals were tall, with arm spans wider than their heights.[2] In Pubmed, literature search for occurrence of EDS –type VIII with Café –au-lait macules was done and the results showed association of Café–au-lait macules with type I, IV and type V but not with Type VIII EDS.[4]

EDS – Type VIII is a very rare type of EDS and only a few cases have been reported. In our case, periodontitis, pretibial plaque, moderately hyper-extensible skin and joints of hands with rocker bottom foot, and arm span more than height was seen. Along with the above findings, we also noted Café- au – lait macules which can be considered as a new variant. Short height was noted as compared to tall individuals in EDS.