Cooks Syndrome: A Case Report and

Brief Review

Abstract: Congenital anonychia is rare, particu-larly when all 10 toenails are absent. When anonychia isassociated with absence of distal phalanges, a diagno-sis of Cooks syndrome must be considered. We presenta case and discussion of a patient with congenitalanonychia, absent distal phalanges, and rudimentaryhypoplastic middle phalanges and brachydactyly,consistent with Cooks syndrome.

A 2-year-old African American girl presented to ourclinic for evaluation of a pigmented lesion on her rightplantar foot, and an excisional biopsy was arranged. Onfurther physical examination we observed the completeabsence of toenails (Fig. 1) and brachydactyly andanonychia of the fourth digit of her right hand (Fig. 2).She was born with these abnormalities. She was born atfull term and met all of her developmental milestones.Her parents are unrelated, and there are no familymembers with similar findings.

A radiograph of her right foot demonstrated completeabsence of distal phalanges of digits 1, 4, and 5, with rudi-mentary distal phalanges of digits 2 and 3. There washypoplasiaof allmiddlephalanges (Fig. 3).With thephy-sical examination findings of congenital anonychia andthe radiologic evidence of phalangeal absence and hypo-plasia,wediagnosedourpatientwithCookssyndrome.

DISCUSSION

Anonychia, or absence of nails, is rare (1). Anonychiamay be acquired or congenital. Acquired anonychiamay

occur after trauma to the nail matrix, with certain med-ications, or in a variety of skin conditions (1). Anony-chia-onychodystrophy with phalangeal hypoplasia mayoccur with multiple congenital syndromes (Table 1)(2,3). Without the development of distal phalanges, nailformation is unlikely.According toSeitz et al, regulatoryproteins signal the formation of the bony mesenchymalcondensation that forms the distal phalanx,which occurssimultaneously with the development of the nail folds.Nail growth is closely associatedwith the size of the distalphalanx, because nail growth is faster with a largerphalanx (3). Therefore, there is interdependence betweenthe phalangeal bones and nail formation.

Cooks et al (4) first described a family with ‘‘onych-onychia’’ and absence or hypoplasia of distal phalangesin 1985. In the hands, the individuals had progressivehypoplasia of nails 1 to 3, absence of nails 4 and 5, andbrachydactyly of the fifth digit. In the feet, they hadabsence of all toenails and hypoplasia of distal phalanges(4). The authors reported seven affected people in twogenerations and suspected an autosomal-dominant

DOI: 10.1111/j.1525-1470.2011.01668.x

Figure 2. Brachydactyly and anonychia of the fourth digit ofher right hand.

Figure 1. Complete absence of toenails with bulbous-shaped digits.

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inheritance pattern following an initial spontaneousmutation (4,5).

Microduplications on chromosome 17q24.3, a non-coding element of the Sox9 gene, have recently beenassociatedwithCooks syndrome in four patients (7). TheSox9 gene is known to be imperative for chondrocytedifferentiation and cartilage formation (7). A geneticsevaluation was obtained. Karyotype did not reveal anychromosomal abnormalities. Microarray testing formicroduplication at 17q24.3 was normal in our patient,suggesting no abnormalities of herSox9 gene.Webelieveour patient meets the clinical criteria for Cooks syn-drome with phenotypic variant because of the completeanonychia of her toenails, lack of distal phalanges in herfeet, and minimal involvement of her hands. The preva-lence of the microduplication in patients with Cooks

syndrome phenotypes is unknown. Perhaps our patienthas a defect that affected the signaling proteins involvedin distal phalanx formation, which in turn caused heranonychia.

REFERENCES

1. Hawsawi KA, Al Aboud K, Alfadley A et al. Anonychiacongenita totalis: a case report and review of the literature.Int J Dermatol 2002;41:397–399.

2. Baran R, Juhlin L. Bone dependent nail formation. Br JDermatol 1986;114:371–375.

3. Seitz CS, Hamm H. Congenital brachydactyly and nailhypoplasia: clue to bone-dependent nail formation. Br JDermatol 2005;152:1339–1342.

4. Cooks RG, Hertz M, Katznelson MBM et al. A new naildysplasia syndromewith onychonychia and absence and ⁄orhypoplasia of distal phalanges. Clin Genet 1985;27:85–91.

5. Nevin NC, Thomas PS, Eedy DJ et al. Anonychia andabsence ⁄hypoplasia of distal phalanges (Cooks syndrome):report of a second family. J Med Genet 1995;32:638–641.

6. Castori M, Brancati F, Mingarelli R, Mundios S, Dalla-piccola B. A novel patient with Cooks syndrome supportssplitting from ‘classic’ brachydactyly type B. Am J MedGenet A 2007;2:195–199.

7. Kurth I, Klopocki E, Stricker S et al. Duplications of non-coding elements 5¢ of SOX9 are associated with brachy-dactyly-anonychia. Nat Genet 2009;41:862–863.

Christina B. Brennan, M.D.*Tara Buehler, B.S.�Jack L. Lesher, Jr., M.D.**Section of Dermatology, �Medical College of Georgia,Georgia Health Sciences University, Augusta, Georgia

TABLE 1. Syndromes with Congenital Hyponychia or Anony-chia and Phalangeal Hypoplasia

Syndrome Clinical features

Cooks syndrome Fingernail hypoplasia or completeabsence of fingernails; total absence of alltoenails; hypoplasia of distal phalangesin hands; absence of all distal phalangesof feet (4,5)

Brachydactyly B Amputation-like lesions of digits;hypo ⁄ aplasia of distal phalanges, nailhyponychia or anonychia; in the‘‘classic’’ form, thumbs spared, but mayappear broadened or bifid in severecases (6)

Brachydactyly A5 Absence of middle phalanges; variousnail dysplasias of digits 2–5 of handsand feet (3)

Figure 3. Radiograph of right foot demonstrating complete absence of distal phalanges of digits 1, 4, and 5 and rudimentary distalphalanges of digits 2 and 3. Hypoplasia of all middle phalanges is seen.

Address correspondence to Christina B. Brennan, M.D., 1004Chafee Ave, FH-100, Augusta, GA 30912, or e-mail: cbrennan@georgiahealth.edu.

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