Congenital cataract and slowly progressing facial skin lesions in a 5‐year‐old boy

A five-year-old boy presented to our outpatient clinic with asymptomatic skin lesions on the right side of his face. The lesions had first appeared on the lateral cheek during the patient's first year of life and had gradually extended medially. At the age of 10 months, a congenital cataract of the right eye had been diagnosed; a lensectomy was performed, and the child subsequently wore a contact lens. Over time, he developed severe amblyopia and an inward strabismus of the right eye. The mother reported that she had premature contractions in the seventh month of pregnancy, whereupon treatment was administered to promote fetal lung maturation. The child was born at term, and further development was normal. There was no clinical evidence of skeletal, dental, or neurological abnormalities. On physical examination, grouped, blaschkoid-arranged, dimple-shaped follicular openings were present on the right cheek with interspersed open and closed comedones (Figure 1a, b). There was no evidence of inflammation, as neither erythema nor swelling was noted. Apart from minimal white dermographism, the remainder of the skin was unremarkable. Your diagnosis? Diagnosis: Nevus comedonicus syndrome (NCS) Nevus comedonicus syndrome (NCS) was first described by Engber in 1978 and is characterized by the presence of a nevus comedonicus associated with systemic manifestations.1 Regarding the frequency of this rare condition, in a 2012 review, 30 of 349 cases (8.6 %) of nevus comedonicus were found to have additional extracutaneous abnormalities,2 while the prevalence of nevus comedonicus is reported as 1 in 45,000 to 100,000.3 Nevus comedonicus is an epidermal nevus with organoid differentiation of the hair follicle and typically appears at birth, is located unilaterally along the Blaschko lines and most often affects the head-and-neck region.2 The clinical morphology of nevus comedonicus in NCS can be divided into three types. The first is the most common comedonal type with dilated follicular openings filled with dark cornified material, and the second is the Selhorst type with giant comedones, cysts, and extensive scarring. The least frequent type has small pits and scattered comedones and therefore resembles atrophoderma vermiculatum.4 This type was present in our patient, making atrophoderma vermiculatum a valid differential diagnosis. Furthermore, acneiform nevus and mild childhood acne were considered, but both display signs of inflammation that were absent in our patient. Happle-Tinschert syndrome was ruled out due to the lack of basaloid follicular hamartoma and other skin findings. Regarding the extracutaneous manifestations of NCS, these are almost exclusively localized ipsilaterally, usually in close proximity to the nevus, and involve the eye and/or skeleton in more than 50 % of cases. It is striking that, in atrophoderma vermiculatum-type NCS, a congenital cataract is the only or the predominant extracutaneous manifestation in approximately 80.0 % of the cases, as was the case in our patient. Concerning skeletal anomalies, digital malformations are most common, and these are disproportionately associated with the comedonal type. Anomalies of the central nervous system, teeth, soft tissue and cardiovascular system are generally less frequent in NCS.4 At the molecular level, Levinsohn et al. identified somatic gain-of-function mutations in the Never in Mitosis A (NIMA)-related kinase 9 (NEK9) gene as the cause of nevus comedonicus in 2016.5 These mutations led to increased phosphorylation at Thr210, which is localized in the activation loop of NEK9. Impaired follicular differentiation was observed with the presence of the interfollicular epidermis marker keratin 10 and an increase of keratin 15, a marker for the hair follicle bulge. Since then, further NEK9 mutations have been identified in the skin of three other patients with nevus comedonicus and in two patients with NCS.6-8 Interestingly, recessive germline loss-of-function mutations in NEK9 lead to severe deformities and malfunctioning of bones and joints, resulting in disorders such as lethal skeletal dysplasia or arthrogryposis.6, 9 The treatment of nevus comedonicus is primarily for aesthetic reasons and/ or to reduce signs of inflammation, although there is no generally recognized and/or effective treatment. Topical retinoids and, to a lesser extent, systemic retinoids, vitamin D derivatives as well as topical keratolytics, such as salicylic acid, have been used. Furthermore, procedural interventions including dermabrasion, surgical excision, and laser therapies may be considered.3 Since no inflammation and only sparse comedones were present in our patient, retinoids, vitamin D derivatives and/or keratolytics were not promising treatment options. Fractional CO2 laser treatment, analogous to atrophic acne scar therapy to induce collagen remodeling and re-epithelialization, was discussed. However, due to the young age of the patient in combination with possible occurrence of pain during the laser treatment, this was considered a future option.10 Genetic testing of a lesional skin sample and genetic counseling were recommended, but these were not performed due to the lack of immediate consequences. None.