Dermatologic Manifestations of Waardenburg Syndrome Clinical Presentation

Updated: Feb 08, 2019
  • Author: Lyubomir A Dourmishev, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Characteristic morphologic features of Waardenburg syndrome can be recognized immediately or soon after birth. Features typically include white forelock, broad nasal root, and hypopigmented irides. Parents notice that the child does not react to sounds.


Physical Examination

Not every case expresses all clinical manifestations of the complete Waardenburg syndrome, and forme fruste conditions are commonly observed. Based on clinical and genetic criteria, 4 types of Waardenburg syndrome are recognized. All forms show marked variability, even within families. See the images below.

Marked facial asymmetry, lagophthalmos, a drooping Marked facial asymmetry, lagophthalmos, a drooping right corner of the mouth. Image courtesy of Dourmishev LA et al, Cutis 1999; 63:139-40. Copyright 1999, Quadrant Healthcom, Inc.
Visage in profile demonstrates absence of nasofron Visage in profile demonstrates absence of nasofrontal angle, eyebrow hypertrichosis, upturned nasal tip, and shortened upper lip with a pronounced cupid's bow. Image courtesy of Dourmishev LA et al, Cutis 1999; 63:139-40. Copyright 1999, Quadrant Healthcom, Inc.
Brother and sister with Waardenburg syndrome. Imag Brother and sister with Waardenburg syndrome. Image courtesy of Dourmishev LA et al, Cutis 1999; 63:139-40. Copyright 1999, Quadrant Healthcom, Inc.

Type I Waardenburg syndrome is characterized by evidence of dystopia canthorum and the full symptomatology of the disease. Individuals with type I Waardenburg syndrome also have a narrow nose, marked hypoplasia of the nasal bone, short philtrum, and short and retropositioned maxilla. A discriminant analysis revealed that the inner intercanthic distance, philtrum length, lower facial height, and nasal bone length were discriminating parameters of Waardenburg syndrome. Convergent strabismus (blepharophimosis) and reduced visibility of the medial sclera is observed. The head circumference, clivus length, and facial depth are smaller in affected individuals with this syndrome.

Individuals with type II Waardenburg syndrome are a heterogeneous group with normally located canthi (without dystopia canthorum). Sensorineural hearing loss (77%) and heterochromia iridium (47%) are the 2 most important diagnostic indicators for this type. [14, 15]  Other clinical manifestations (eg, white forelock, skin patches) are more frequent in type I.

Type III Waardenburg syndrome (Klein-Waardenburg syndrome) is similar to type I but is also characterized by musculoskeletal abnormalities (ie, aplasia of the first 2 ribs, lack of differentiation of the small carpal bones, cystic formation of the sacrum, abnormalities of the arms [eg, amyoplasia and stiffness of the joints, bilateral cutaneous syndactyly]). Some individuals with type III Waardenburg syndrome are homozygotes. Other clinical manifestations of type III syndrome comprise the full symptomatology of the disease plus mental retardation, microcephaly, and severe skeletal anomalies.

Type IV Waardenburg syndrome (Shah-Waardenburg syndrome) is the association of Waardenburg syndrome with congenital aganglionic megacolon (Hirschsprung disease). [16] Hirschsprung disease affects 1 neonate per 5000 births. See Hirschsprung Disease for more information. [17, 18]

Dystopia canthorum is found in 41.2-99% of persons with Waardenburg syndrome. [13]  The distance between the inner angles of the eyelids is accompanied by increased distance between the inferior lacrimal points. Hageman and Delleman divided Waardenburg syndrome into 2 variants: with dystopia canthorum and without.

Congenital deafmutism occurs in 9-62.5% of persons with Waardenburg syndrome. Different combinations of hearing loss occur: unilateral or bilateral, severe or moderate, total or moderate. Fisch separated Waardenburg syndrome into the following distinct types according to audiogram results:

  • Patients with total deafness and little residual hearing at the lower frequency

  • Patients with a moderate degree of deafness with uniform hearing loss in the lower and middle frequency with improvement in the higher frequency

Overall, 100% of patients with hearing loss and Waardenburg syndrome have temporal bone anomalies on at least one measurement of their inner ear and 50% have an enlargement of the vestibular aqueduct at the mid point. [19] As shown by computed tomography, enlargement of the vestibular aqueduct and the upper vestibule, narrowing of the internal auditory canal porus, and hypoplasia of the modiolus are features of Waardenburg syndrome.

Pigmentary abnormalities in Waardenburg syndrome affect skin, hair, and eyes. Cutaneous color abnormalities are observed in 8.3-50% of patients and include the following types of lesions:

  • Achromic spots with sharply defined, irregular borders and with hyperpigmented islands scattered throughout, resembling those of piebaldism

  • Hyperpigmented macules on normally pigmented skin, which have been described as "patchy skin" and giving a "dappled appearance"

Pigmentary disturbances of hairs in Waardenburg syndrome include 2 types of alterations: white forelock and premature graying of scalp hair, eyebrows, cilia, or body hair. The white forelock is observed in 17-58.4% of persons with Waardenburg syndrome and involves the forehead (and both medial eyebrows), the vertex, or another part of scalp. The white forelock may be evident at birth or soon afterward, or it may develop later. Poliosis may persist throughout life or may disappear in the first years of life and reappear later. Chang et al [20] reported 2 members of a family with Waardenburg syndrome who atypically demonstrated spontaneous pigmentation and contraction of congenital leukodermic patches. In place of a white forelock, an artificial color of red, brown, or black hair was observed. Patients with Waardenburg syndrome become prematurely gray in 7% of cases.

Ocular color abnormalities of Waardenburg syndrome include 3 types of disturbances, as follows:

  • Heterochromia (different color) iridis: Heterochromia iridis, partial or complete, was found in 21-28% of patients with Waardenburg syndrome.

  • Bilateral isohypochromia iridis (pale blue eyes): Pale blue eyes in Waardenburg syndrome are observed in 14.9-42% of patients.

  • Fundus pigmentary alterations: Patients with fundus pigmentary abnormalities may have 2 types of defects: a generalized decrease in retinal pigment (albinotic fundi) and a pigment mottling in the periphery.


A characteristic facial appearance of patients with Waardenburg syndrome and facial asymmetry in various levels of manifestation has been observed. Hyperplasia of the root of the nose is reported in 17.6-78% of persons with Waardenburg syndrome. Hypertrichosis of the medial eyebrows is reported in 17.6-69% of persons with Waardenburg syndrome. Patients with Waardenburg syndrome and facial palsy from age 7 years and lingua plicata (2 main features of the classic triad of Melkersson-Rosenthal syndrome) have been observed. [21]

Various other abnormalities have been described, including central nervous system features (eg, mental retardation, seizures, psychic disturbances), renal agenesis, [22]  skeletal and muscular defects (eg, macrocephaly or microcephaly, osseous cysts, syndactyly, spina bifida), skin and hair manifestations (eg, localized hypertrichosis, palmoplantar hyperkeratosis), and eye features (eg, strabismus, cataracts, palpebral ptosis, epicanthus),

A severe type designated anophthalmia-Waardenburg syndrome presents with bilateral anophthalmia, cerebral malformations, epilepsy, limb anomalies, and mental retardation in addition to skin lesions. [23]