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Witkop syndrome: A case report of an affected family

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Witkop syndrome: A case report of an affected family
Vinod Kumar Khurana MD, Rakesh Kumar Gupta MD, Lekshmi P Kumar MD
Dermatology Online Journal 18 (6): 2

Hindu Rao Hospital, Delhi, India


We report a family affected with Witkop tooth and nail syndrome. This is a rare syndrome among the ectodermal dysplasias in which there are abnormalities of teeth, nails, and hair with normal sweat gland function.


Witkop tooth and nail syndrome was first reported by CJ Witkop in 1965 [1]. It is an ectodermal dysplasia primarily presenting with dysplasia of nails and hypodontia, with unaffected sweat gland function [1, 2]. Chitty et al consider the term a misnomer because hair was involved in the original as well as later case reports [3].

The syndrome is transmitted by autosomal dominant inheritance [3, 4, 5, 6]. The gene involved was identified in 2001, and is known as the MSX1 gene [5, 6]. MSX1 is the official symbol for the muscle segment homeobox gene-1, which encodes a nonclustered homeobox protein [6, 7]. The gene located in chromosome 4, is important for development of teeth and nails [5, 6, 7]. MSX1 is expressed in neural crest derived mesenchyme in the mandibular and maxillary processes of the first branchial arch and also in the nail bed mesenchyme [5, 6]. A nonsense mutation in MSX1 causes Witkop syndrome [6, 7].

Case report

Two sisters of age 20 and 16 years presented with complaints of having small deformed teeth, brittle nails, and reduced hair growth. Both the sisters gave a history of delayed dentition. Few milk teeth fell out in the younger sister while none fell out in the elder one. Both have very slow nail and hair growth. There is no history of heat intolerance or disturbance of sweat gland functioning.

Born out of a nonconsanguinous marriage, they were normal at birth and their mother had uneventful pregnancies. There was no history of colloidon membrane at the time of birth. Milestones were appropriate for age and there is no mental retardation.

The family consists of both parents and four children; the other two siblings and the mother are unaffected (Table 1).The father has widely spaced teeth and longitudinal ridging of nails. The parents report that their relatives are unaffected.


Figure 1aFigure 1b
Figure 1a. Dentition of elder sister: Widely spaced peg shaped teeth

Figure 1b. Dentition of younger sister: Widely spaced peg and cone shaped teeth

Figure 2aFigure 2b
Figure 2a. Toenails of elder sister showing ridging and koilonychia

Figure 2b. Toenails of younger sister showing koilonychia of 3rd and 4th nails of both feet

Figure 3aFigure 3b
Figure 3a. Fingernails of younger sister: Normal in appearance

Figure 3b. Fingernails of elder sister showing ridging and onycholysis

Figure 4
Figure 4. Scalp of elder sister: Note thinning of hair and reduced growth

Both have a reduced number of teeth, which are widely spaced and peg or cone shaped (Figures 1a and 1b). The elder sister has total agenesis of permanent teeth, whereas the younger sister has partial agenesis. In both sisters the mandible appeared to be smaller than normal. The toenails are affected in both sisters showing koilonychia and ridging (Figures 2a and 2b). Fingernails are normal in the younger sister (Figure 3a), whereas the elder sister has ridging and onycholysis in all fingernails (Figure 3b). Palms and soles in both sisters show hyperlinearity, but no keratoderma. Skin is pale and dry with follicular prominence. Both have hair just to the nape of neck (Figure 4). They have sparse eyebrows, body hair, and secondary sexual hair. We performed a hair shaft study, which was normal. An orthopantamogram showed persistence of deciduous teeth (Figures 5a and 5b). KOH mount and fungal culture were done on the nail clippings of the elder sister and fungal elements were detected; the patient is on antifungal treatment.

Figure 5aFigure 5b
Figure 5a. OPG of elder sister showing all milk teeth

Figure 5b. OPG of younger sister showing both milk and permanent teeth


Witkop syndrome affects teeth, nails, and hair, but there is sparing of sweat gland function. The teeth of individuals affected are widely spaced, conical, and narrow-crowned [8, 9, 10]. There may be partial or total agenesis of permanent dentition and this can result in prolonged retention of primary teeth [2, 11]. Nails are slow growing and show koilonychia and ridging [1, 2, 3, 4, 5, 8, 9]. In some instances, marked longitudinal ridges and pitting are the only features [5]. Toenails are usually more affected than fingernails [3, 4, 5, 10, 11]. The nail changes are known to improve with age [3, 4, 5, 10, 11]. Hair is normal in distribution, though fine and sparse with reduced growth [3, 10, 11]. Dry skin and follicular papules are also documented in a few cases [1, 3, 4]. Abnormalities of eyebrows and eyelashes are variable features in this syndrome [3].

Our patients have teeth, nails, and hair changes consistent with the description of Witkop syndrome. The elder sister has total agenesis whereas the younger sister has partial agenesis of permanent teeth. Both have widely spaced peg and cone shaped teeth. Fingernails are spared in the younger sister whereas toenails are affected in both. Hair growth is very much reduced in both sisters but the younger sister has denser scalp hair. Sweating is normal in both. The father has a complete set of teeth, but they are widely spaced; he has longitudinal ridging of the toenails.

Witkop syndrome is transmitted by autosomal dominant inheritance, caused by a nonsense mutation in the MSX1 gene [5, 6]. The sisters could have inherited the disease from their father. The elder sister is more affected than the younger sister because she has less hair, abnormalities of both toenails and fingernails, and total agenesis of permanent dentition. Fungal elements were isolated from the fingernails of the elder sister and this could be a coincidental finding. The other two siblings were normal. In addition, variable penetrance and expression has been reported [3, 4, 5, 10]. There is also considerable variation of clinical findings in gene carriers [3, 4, 5, 6]. Jumlongras et al suggest a role of modifier genes because MSX1 is known to interact with several other regulatory proteins [5]. Other factors, probably environmental, can modulate the effects of MSX1 mutations [5, 6].

Skin changes such as follicular prominence and dry skin seen in our patients were also reported as an association in this syndrome [3, 4].

No typical facial appearance is associated with Witkop syndrome [4]. Jumlongras et al in their study noted smaller than normal maxillae and mandibles in their patients [5]. Our patients also appear to have smaller mandibles.

The severity of oligodontia varies from mild to extreme [2, 8, 9]. The nail dysplasia is known to ameliorate with age [3, 5, 11]. For these reasons, the syndrome is difficult to detect in adults and is now considered to be more common than previously thought [11, 12]. Isolated cases without a family history have also been reported [10, 12].

Other differential diagnosis included Fried TNS and Tricho-onychodental syndrome [3, 4, 10, 11, 13]. Both are very similar to Witkop. Fried TNS may represent an autosomal recessive form of this condition [4, 11]. Moreover, Fried TNS involves significance sparseness and thinning of hair and eyebrows as well as everted lips [4, 9, 10, 11]. TOD (Tricho-onychodental syndrome), reported in a Japanese family, is also very similar but has hypohidrosis as a feature [13]. Our patients did not have deafness or mental retardation found in DOOR Syndrome (Deafness and onycho osteodystrophy with mental retardation) or polydactly as seen in Curry-Hall Syndrome [4, 10]. Palmoplantar hyperkeratosis is frequent in Clouston syndrome and the absence thereof and the prominence of tooth involvement in our patients helped to distinguish between Clouston and Witkop Syndrome [3, 11, 14]. Rapp-Hodgkin Syndrome is associated with cleft palate and MSX1 gene mutation is known to cause cleft palate, but in this condition the hair is mostly sparse and friable and histologically shows pili torti [3, 11, 14].

The management of patients with Witkop syndrome requires orthodontic treatment to restore the facial aesthetics [10]. Genetic counseling is beneficial for affected individuals and their families [4, 5]. The nails usually require no treatment [14]. Memarpour et al suggest lubrication of nails and trimming to keep them short and smooth to avoid fungal infections [4]. One of our patients also had associated onychomycosis and is on treatment with oral antifungals. Use of hair oil is suggested to reduce hair dryness in patients with this condition [4, 9].


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