EEC Syndrome - Story

 

Definition

The syndrome Ectrodactyly-ectodermal dysplasia-cleft palate (EEC) is a rare congenital malformation pathology characterized by the association of ectrodactyly (anomaly limb in which some central rays of the hands are missing with appearance of "clamp hand" or "crab claw hand"), abnormalities of the palate and abnormalities of the tissues ectodermal derivation. The ectoderm is the package outer embryonic tissue from which they originally nervous and epithelial tissues covering (epidermis, epithelium corneal etc..) and appendages (hair,nails, etc...)

Signs and Symptoms

Concerning the facies, frequent abnormalities of the naso-lacrimal duct, the genitourinary system and major anomalies of the extremities, from ectrodactily to syndactily (fusion of fingers and toes).

A load of facial cleft lip and cleft palate may be at present. The ectodermal part of this syndrome involves hair, teeth and nails. The hypohidrosis is variable, although often the skin is dry and hyperkeratosis may be present the palms of hands and feet. The hair is sparse, clear and dry eyelashes and eyebrows are often lacking. Teeth are small and can be partially formed and there can be hypodontia and anodontia. The nails are thin, fragile and marked; frequently found abnormalities of tear duct. Nardi and colleagues found abnormalities in 13 to 25 genitourinary cases. These abnormalities included: megaureter, vescicoureteric reflux, hydronephrosis and hypospadias. Mental development is usually normal, the cleft, in most cases in the form of cleft lip and palate, is frequent, but not essential part of the syndrome. All features are highly variable and must be placed carefully examining and advise the parents of the patient, who may appear as an isolated case. Van Maldergem, Kuna and colleagues revealed an abnormal hypothalamic-pituitary function. (R. M. Winter, M. Baraitser, London Dysmorphology Database, Oxford Medical Databases, 2000). The ocular manifestations are a component found frequently in EEC syndrome. (Ireland et al. Ophthalmic Manifestations of ectodermal dysplasia-ectrodactyly-clefting syndrome. Ophthalmic-plast, reconstr-surg. 1998, 14 / 4 (295-297) and (Colin Willoughby, unpublished data).

Etiology

The disease is linked to gene mutations p63, deputy the production of a protein essential for both (i) during the embryogenesis of the normal developement of the ectoderm, and (ii) in adult for the maturation and differentiation of the staminal cells of various epithelial tissues including cornea, where the 'expression of p63 is restricted at the basal layer of the limbus, the niche cells corneal stem cells and stem cells when cultured laboratory(Figg. 8a, 8b). Most cases are sporadic, associated with de novo mutations, which typically arise during the development of 'embryo. Familial cases show a type of autosomal dominant inheritance variable penetrance.

The incidence and the prevalence of the disease in the Italian population not are known. Males and females are equally affected.

Fig. 8a

figura 8a

 

Fig. 8b

figura 8b

 

Eye problems

During childhood the main features that put at a disadvantage a patient suffering from EEC syndrome are cleft palate and deformities of the hand with its surgical corrections. During young adulthood, however, the eye problems become prevalent aspects of disability: patients often show alterations of the ocular surface (blepharitis and conjunctivitis), dysfunction of corneal epithelium and poor re-epithelization following trauma and penetrating keratoplasty (Fig.9).

 

Fig.9

figura 9

 

These patients have a vascularized corneal pannus that leads to a progressive decrease of vision to complete loss of vision (Figg.10a, 10b).

Fig.10a
Fig.10b
Fig.11
figura 10a
figura 10b
figura 11

 

Once this process occurred, the penetrating keratoplasty has a poor prognosis because the eye problems are caused (i) by atresia of lacrimal ducts and glands of Meibom absence (Fig.11), involving a deficiency of the tear film, (ii) corneal epithelial defects caused by mutations in the p63 gene, the necessary and essential for corneal stem cells can maintain and ensure the regeneration of the epithelium of the cornea, or in response the physiological need of renewal, both in case of damaging insults that require repair of the ocular surface.

Therapies

While the 'tear film instability and symptoms of' dry eye can be mitigated and / or resolved by the use of artificial tears or lubricating the ocular surface, which should be administered regularly to support the tear film deficient, for defects epithelial currently no curative treatments. Therefore the only alternative for the treatment of such defects is to use strips of corneal epithelium (obtained by in vitro cultivation of corneal stem cells-Cellular Therapy)) genetically corrected (Gene Therapy).

Researchers FBOV:
Di Iorio Enzo, Barbaro Vanessa, Ferrari Stefano