Oculodentodigital Dysplasia, Autosomal Recessive

A number sign (#) is used with this entry because of evidence that autosomal recessive oculodentodigital dysplasia is caused by homozygous mutation in the GJA1 gene (121014) on chromosome 6q22.

Oculodentodigital dysplasia is usually inherited as an autosomal dominant disorder (164200), which is also caused by mutation in the GJA1 gene.

Clinical Features

Traboulsi et al. (1986) proposed the existence of a recessive form of oculodentoosseous dysplasia with more severe ocular affection than in the dominant form. They described a single case in a girl with unaffected first-cousin parents. The patient showed long, narrow nose with hypoplastic nasal alae, telecanthus, prominent epicanthal folds, microphthalmia, microcornea, malformed teeth with abnormal enamel, syndactyly of fingers 4 and 5 with clinodactyly of the distal phalanx of the fifth finger in each hand, and soft tissue syndactyly of toes 2, 3, and 4. The iris was markedly dysplastic. Remnants of the hyaloid system bridged from the optic nerve head to the posterior surface of the lens. Skeletal changes included markedly obtuse mandibular angle, widening of the long bones of the limbs, and strikingly wide diaphyses in the bones of the hands and feet. Recessive inheritance might be considered also in the case of the brother and sister pairs reported by Gillespie (1964) and Eidelman et al. (1967). Regarding the alternative possibility of a new dominant mutation in the case of Traboulsi et al. (1986), paternal age was not provided.

Beighton et al. (1979) reported 3 Afrikaner patients with ODDD in 2 kindreds of Dutch descent. Two of the patients were double first cousins, the products of marriages between a pair of brothers and a pair of sisters who were themselves unaffected. All 3 patients had a similar facial appearance and typical ocular and digital abnormalities. In addition, they showed cranial hyperostosis and mandibular overgrowth. Two had serious neurologic complications from spinal cord compression at the base of the skull and calcification of the basal ganglia. Beighton (1997) considered an autosomal recessive form of ODOD to be adequately documented.

Richardson et al. (2006) reported 2 sisters, the offspring of consanguineous Pakistani parents, with ODDD. The proband was noted at birth to be hypotonic with large fontanels and widely separated sutures, small deep-set eyes, a pinched nasal appearance with hypoplastic alae nasi, and micrognathia. She had complete skin syndactyly of the left ring and little fingers and the right middle, ring, and little fingers. Ophthalmologic assessment showed bilateral microphthalmia, persistent pupillary membrane, and cataract. Tooth eruption was delayed and her deciduous teeth, which were severely hypoplastic, were removed at age 3 years because of chronic abscesses. She had sparse, fine hair, which did not appear until age 2 years. She had gross motor and speech delay. Her sister had a similar facial appearance and bilateral syndactyly of her ring and little fingers. At age 1 year, she still had no teeth. She was not delayed in her gross motor milestones.

Damiano Salpietro et al. (2004) reported a 10-year-old boy with what they considered to be Hallermann-Streiff syndrome (HSS; 234100). He was the second child of healthy, unrelated parents and showed short stature, a distinctive triangular face, a brachycephalic head with frontal bossing, sparse curly and thin scalp hair, hypoplastic eyebrows, and short, downslanted palpebral fissures with telecanthus and sparse eyelashes. Hands and feet were small with clinodactyly of 5th fingers. He had mild psychomotor retardation, dental anomalies, and myopia. The boy also showed deficiency of growth hormone and insulin-like growth factor-1. Hennekam et al. (2010) stated that this patient 'clearly had oculo-dento-digital syndrome.'

Molecular Genetics

In 2 sisters with autosomal recessive ODDD, Richardson et al. (2006) identified homozygosity for a nonsense mutation in the GJA1 gene (121014.0016).

In the patient described by Damiano Salpietro et al. (2004) as having Hallermann-Streiff syndrome but who was later determined to have ODDD (Hennekam et al., 2010), Pizzuti et al. (2004) identified a homozygous mutation in the GJA1 gene (121014.0017).