Coltro, Pedro S.

Ferreira, Marcus C.

Fonseca, Alexandre S. F.

Friedhofer, Henri

Ocharan, Alan M. W.

Sturtz, Gustavo P.

English

Cadernos Espinosanos (E-Journal)

171CLINICS 2006;61(2):171-4Division of Plastic Surgery, São Paulo University Medical School - São Paulo/SP.Email: alexandrefonseca@terra.com.brLETTER TO THE EDITORSURGICAL TREATMENT FOR EYELID DEFORMITY INCROUZON SYNDROME ASSOCIATED WITHACANTHOSIS NIGRICANS: CASE REPORTHenri Friedhofer, Alan M. W. Ocharan, Gustavo P. Sturtz, Alexandre S. F. Fonseca, Pedro S. Coltro, and Marcus C.FerreiraThe combination of Crouzon syndrome with acantho-sis nigricans is unusual. The incidence of this combinationis still uncertain, and there are only 30 cases reported inthe medical literature.1–3 Crouzon syndrome is caused bymutation of the gene FGFR3 (fibroblast growth factorreceptor 3). In this gene, other mutations can cause a kindof nanism that is lethal during the first weeks of life. Re-cent biomolecular studies have indicated that the associa-tion of Crouzon syndrome with acanthosis nigricans shouldbe considered as a different pathology, as opposed toCrouzon syndrome in isolation, because acanthosisnigricans would originate from a different gene and froma diverse chromosome mutation.4 Crouzon syndrome is anautosomal dominant disease that involves craniosynosto-sis, exophthalmia, hypoplasia of the middle third of theface, and irregularities of dental occlusion. Its incidenceis about 1 in 300,000 live births.Acanthosis nigricans is a rare illness related to the skin.It is characterized by hyperplasia and hypertrophy, withhyperkeratosis and slight hyperpigmentation on the innerskin layer, without melanocytic hyperplasia. The epidermispresents as a wavy surface (Figure 2). It can affect the neck,armpits, normally folding areas, and the orbital region. Theetiology of acanthosis nigricans is variable and can be oneof the following:- Hereditary with dominant autosomal transmission.- Associated with genetic abnormalities or endocrine dis-eases.- Pseudo-acanthosis nigricans resulting from complica-tions of obesity.- Induced by medications.- Combined with cancer, usually gastrointestinal adeno-carcinoma.The association of acanthosis nigricans with Crouzonsyndrome creates a phenotypic pattern. All patients thathave been described in medical literature have had an ex-cess of skin and hyperpigmented lesions in the orbital area,predominantly on the lower eyelid, and on the peroral area,neck, and armpitsCASE REPORTThe patient, a 25-year-old woman, presented with a skinexcess and hyperpigmentation on the lower eyelid. Thesealterations had started during her teenage years. Crouzonsyndrome was diagnosed after her birth, and when she was3 years old, she underwent craniosynostosis correction. Bythe time of the physical exam, the patient presentedexophthalmia, hypertelorism, craniofacial deformities, hy-poplasia of the middle third of the face, intensehyperpigmentation of the armpits, cervical region, oral,nasolabial, and upper and lower eyelid creases. The skinwas irregular and thick. (Figure 1). The lower eyelid fis-sures were oblique, and there was skin excess on the lowerand upper eyelid on both sides, primarily on the lower eye-lids. The lateral retinaculum was medially displaced, andthe upper eyelids were 4 mm below the scleral edge. Theseare characteristics of a slight eyelid ptosis associated withtelecanthus. The adipose bags were more evident on thelower eyelids (Figure 1).A cutaneous blepharoplasty was performed through re-section of skin and preaponeurotic fat (resulting in addi-tional soft-tissue reduction and volume depletion), and bi-lateral canthal suspension was performed (Figure 3). Thelateral retinaculum was sutured with EthibondTM 4-0 to thereversed border of the periosteum. The continuousMononylon TM 6-0 cutaneous suture was removed 5 dayslater. The scars healed in a widened and depressed patternon the upper eyelid and on the lateral lower portion.Microscopic histological examination revealed hyper-keratosis of the epidermis, acanthosis with widening of theepithelial cones, and papillomatosis, which can be de-scribed as acanthosis nigricans (Figure 2). The orbicular172CLINICS 2006;61(2):171-4Surgical treatment for eyelid deformity in crouzon syndromeFriedhofer H et al.muscular tissue and the periorbital fat did not exhibit his-tological alterations.DISCUSSIONSome characteristics of the association of Crouzon syn-drome and acanthosis nigricans differ from cases of iso-lated Crouzon syndrome. There is a greater frequency ofisolated Crouzon syndrome occurring in men, while the as-sociation of Crouzon syndrome with acanthosis nigricansoccurs more frequently in women, at a 9:2 ratio. The phe-notype of these patients is very similar, with skin wrinklesand hyperpigmentation of the orbital region. When thesecharacteristics occur in combination with Crouzon syn-drome, the patients look much more alike one another. Inisolated acanthosis nigricans, the face is not the most af-fected area. In the association of the two diseases, the pero-ral, paranasal, and eyelid areas are affected in almost allpatients. It is possible that this happens because of the mid-dle third facial hypoplasia that is characteristic of Crouzonpatients.The cause of acanthosis nigricans and its skin effectsare not yet well established. In malignant acanthosisnigricans, there is secretion of a tumor polypeptide that islike epidermal growth factor. In association with endocrinedisease and obesity, insulin resistance has been reported,such as that found in hyperandrogenism, Cushing syn-drome, Addison disease, and hypothyroidism. Insulin re-sistance causes an excess of insulin, and when it binds withinsulin and insulin-like receptors, it produces keratinocytegrowth factor, leading to epidermal cellular proliferation.3The association of Crouzon syndrome and acanthosisnigricans can be caused by a genetic defect that inducescraniosynostosis and acanthosis nigricans. Recentbiomolecular and genetic studies that analyzed the genotypeof patients with both pathologies have revealed a mutationof the gene responsible for the fibroblastic receptor 3 tran-scription, located in chromosome 4.3,5 Studies of patients withisolated Crouzon syndrome revealed only a mutation of thegene responsible for the fibroblastic 2-receptor transcription,located in chromosome 10. These data support the idea thatthe association of Crouzon syndrome with acanthosisnigricans must be considered as a different pathology.4In relation to the treatment of the craniofacial anddermatologic alterations found in these cases, craniosyn-ostosis brought no improvement in the acanthosis, leadingus to believe that those skin alterations are not secondaryto the central nervous system changes that usually occurduring the natural history of Crouzon syndrome.6There are only 2 previously reported cases of the asso-ciation of Crouzon syndrome with acanthosis nigricans inwhich the patients underwent skin resection on the eyelid.There is no report of complete blepharoplasty withcanthopexy. Blepharoplasty and lateral canthal suspension,using the conventional cutaneous technique, is effective inproducing aesthetic improvement of the cosmetic blemishesin the eylid area caused by this pathology, because this pro-Figure 2 - The hyperplasia of the corneal extract can be seen in greaterdetail along with an increased number of keratinocytes, an increase of thepapillary dermis, and an extension of the dermal papillae. These alterationsare characteristics of acanthosis nigricans (hemotoxylin and eosin 50x)Figure 1 - Preoperative view showing a cutaneous excess on the lower eyelidbefore resection of the upper eyelid skin and lateral canthal suspensionFigure 3 - Final results after 1 year. Lateral canthal suspension provided abetter lower eyelid position because it pulled and suspended its components,and it especially stabilized the lower eyelid with the orbit periosteum173CLINICS 2006;61(2):171-4 Surgical treatment for eyelid deformity in crouzon syndromeFriedhofer H et al.cedure allows a greater amount resection of affected eye-lid skin.In the present case following blepharoplasty and lateralcanthal suspension, the upper eyelid scars and the lateralportion of the lower ones became widened and depressed,possibly due the existing histological alterations. However,the obliquity of the eyelid fissure was improved, in spiteof all the difficulties imposed by the caseREFERENCES1. Nagase T, Nagase M, Hirose S, Ohmori K. Crouzon syndrome withacanthosis nigricans: case report and mutational analysis. Cleft PalateCraniofac J. 2000;37:78-82.2. Koizumi H, Tomoyori T, Sato KC, Ohkawara A. An association ofacanthosis nigricans and Crouzon syndrome. J Dermatol. 1992;19:122-6.3. Lapunzina P, Fernandez MC, Varela Junquera JM, Arberas C, Tello AM,Gracia Bouthelier R. Crouzon’s syndrome with acanthosis nigricans.An Esp Pediatr. 2002;56:342-6.4. Cohen MM Jr. Let’s call it “Crouzonodermoskeletal syndrome” so wewon’t be prisoners of our own conventional terminology. Am J MedGenet. 1999;84:74.174CLINICS 2006;61(2):171-4Surgical treatment for eyelid deformity in crouzon syndromeFriedhofer H et al.5. Meyers GA, Orlow SJ, Munro IR, Przylepa KA, Jabs EW. Fibroblastgrowth factor receptor 3 (FGFR3) transmembrane mutation in Crouzonsyndrome with acanthosis nigricans. Nat Genet. 1995;11:462-4.6. Breitbart AS, Eaton C, McCarthy JG. Crouzon’s syndrome associatedwith acanthosis nigricans: ramifications for the craniofacial surgeon.Ann Plast Surg. 1989;22:310-5.

Surgical treatment for eyelid deformity in Crouzon syndrome associated with acanthosis nigricans: case report

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Surgical treatment for eyelid deformity in Crouzon syndrome associated with acanthosis nigricans: case report

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