Odontoonychodermal Dysplasia

A number sign (#) is used with this entry because of evidence that odontoonychodermal dysplasia (OODD) is caused by homozygous or compound heterozygous mutation in the WNT10A gene (606268) on chromosome on chromosome 2q35.

Clinical Features

In 3 consanguineous Lebanese Muslim Shiite sibships, Fadhil et al. (1983) described an apparently 'new' form of ectodermal dysplasia with dystrophic nails, misshapen teeth, including peg-shaped incisors, and erythematous lesions of face and thickening of the palms and soles which showed hyperhidrosis. The hair was unaffected in some but was described as dry and sparse with thinning of the eyebrows in others. The 3 sibships contained 24 children of whom 7 were affected.

Arnold et al. (1995) described a sporadic case. The 31-year-old man was born of nonconsanguineous parents. He complained of progressive thickening of the palmar skin with painful chaffing and increased sweating. Hypodontia with persistence of deciduous teeth was found. There was mild mental deficiency.

Zirbel et al. (1995) described an 11-month-old male infant of nonconsanguineous parents who had atrophic malar plaques that reddened with heat, nail dystrophy, sparse hair, lingual concavity of the incisors, a bifid maxillary incisor, a 5-cusped molar, and hyperhidrosis of the palms and soles. In addition, he had chronic tearing, photophobia, blepharitis, and a mild keratitis. Zirbel et al. (1995) concluded that the child most resembled patients with odontoonychodermal dysplasia, although his eye findings were unique.

Megarbane et al. (2004) reported 3 patients, 2 Lebanese Muslim Shiite brothers and their maternal cousin, who presented with dry hair, pilar keratosis, severe hypodontia, smooth tongue, onychodysplasia, and keratoderma and hyperhidrosis of palms and soles. Molecular analysis excluded X-linkage, suggesting instead autosomal recessive inheritance. The parents denied direct consanguinity but all members of the family originated from the same village.

Bohring et al. (2009) reported 12 patients from 11 unrelated families of German and Turkish origin with ectodermal dysplasia due to confirmed WNT10A mutations. A brother and sister from 1 family had oligodontia and sparse body hair and eyebrows as their only manifestations, and a female proband from another family had cysts of the eyelids in addition to hypodontia, hypotrichosis, palmoplantar keratosis, and dystrophic nails (Schopf-Schulz-Passarge syndrome; 224750). Three patients had photophobia, which was previously described in a patient with OODD by Zirbel et al. (1995). The proband with SSPS was also diagnosed with a porocarcinoma of the left heel. Bohring et al. (2009) suggested that patients with OODD might also be at increased risk for skin tumors. The most consistent finding in all cases and the most specific diagnostic criterion was severe oligodontia of the permanent teeth with normal or less-affected deciduous dentition, involving conical front teeth or agenesis of the upper lateral or central incisors. The authors noted that this pattern of tooth anomalies was similar to that seen in selective tooth agenesis-4 (STHAG4; 150400) and anodontia of permanent teeth (206780), dominant and recessive dental traits, respectively. Despite the high degree of variability in phenotypic expression, Bohring et al. (2009) stated that there was no recognizable genotype/phenotype correlation.

Mapping

Adaimy et al. (2007) studied 3 consanguineous Lebanese Muslim Shiite families that included 6 individuals affected with odontoonychodermal dysplasia. Using a homozygosity mapping strategy, they assigned the disease locus to a region of approximately 9 cM at 2q35-q36.2, with a maximum multipoint lod score of 5.7.

Molecular Genetics

In affected members of 3 consanguineous Lebanese Muslim Shiite families with odontoonychodermal dysplasia, Adaimy et al. (2007) found homozygosity for the same nonsense mutation in the WNT10A gene (E233X; 606268.0001). The mutation was predicted to result in a prematurely terminated protein of 232 amino acids instead of 417 amino acids. One of the families had been reported by Megarbane et al. (2004), and another was a branch of one of the families described by Fadhil et al. (1983). The authors stated that this was the first report of a phenotype related to a mutation in WNT10A and the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, thus expanding the list of WNT-related diseases.

In 12 patients from 11 unrelated families of German and Turkish origin with ectodermal dysplasia, who were known to be negative for mutation in the ectodysplasin-A gene (EDA; 300451), Bohring et al. (2009) identified homozygosity or compound heterozygosity for 5 missense and nonsense mutations in the WNT10A gene (606268.0002-606268.0006). Approximately half of heterozygotes had minor manifestations, and none of the wildtype homozygotes had any symptoms.