Oculodento‐osseous dysplasia: heterogeneity or variable expression?

Abstract

Oculodento‐osseous dysplasia (ODOD) has been recognised in three South African patients from two kindreds of Dutch descent. Their ocular, nasal, dental and digital stigmata resembled those of previously reported cases, but their cranial hyperostosis and mandibular overgrowth were of much greater degree. In addition, the two survivors had serious neurological complications consequent upon spinal cord compression at the base of the skull and calcification of the basal ganglia. Two of the patients were the product of marriages between a pair of brothers and a pair of sisters, who were themselves clinically normal. This situation is best explained by autosomal recessive inheritance. As ODOD is usually transmitted as an autosomal dominant, and in view of the unusual severity of the manifestations in our patients, it is possible that the condition is heterogeneous and that they had a distinct autosomal recessive form of the disorder. The presence of minimal stigmata in the mother and two prior generations of our third patient could be equally well interpreted as representing great variation in phenotypic expression of a single dominant gene or manifestation in a heterozygote for a recessive gene.

A role for Connexin43 during neurodevelopment

“…The authors suggest that all ODDD patients may eventually develop neurological symptoms if they were followed long enough, but another explanation supported by our studies may be that clinical variability in neurological symptoms of ODDD patients is the result of genetic background differences. The genetic background dependent variability of the Shuffler phenotype parallels the variable neurological clinical findings in humans (Beighton et al, 1979;Paznekas et al, 2003). Furthermore, many of the symptoms reported by patients with ODDD may be explained by the Shuffler anatomical de-fects.…”

Variable expression of neurological phenotype in autosomal recessive oculodentodigital dysplasia of two sibs and review of the literature

“…Clinical features are summarised in Table 1. Beighton et al [1] describe neurological symptoms in affected cousins. Similar to our first patient, their second patient was delayed in walking and had persisting mobility problems.…”

“…Interestingly, Timothy syndrome, the association of 4-5 syndactyly, dysmorphism, cardiac arrhythmia and learning disability, is caused by a Beighton et al [1] Traboulsi et al [14] Pizzuti et al [10] Frasson et al [4] Present cases…”

“…2Typical facial features found in oculodentodigital dysplasia neurone involvement with spasticity, hyper-reflexia and positive Babinski sign[1,[6][7][8]12].…”

Autosomal Recessive Oculodentodigital Dysplasia: A Case Report and Review of the Literature

“…The vast majority of ODDD cases described in the literature show an autosomal dominant inheritance pattern and high phenotypic variability [Shapiro et al, 1997;Loddenkemper et al, 2002]. Up to date, 11 patients from 6 families with autosomal recessive ODDD have been reported [Gillespie, 1964;Beighton et al, 1979;Traboulsi et al, 1986;Frasson et al, 2004;Pizzuti et al, 2004;Richard- , 2006], but only 2 of these cases were confirmed by molecular analysis. Pizzuti et al [2004] detected the R76H homozygous missense variant in one of these patients, while Richardson et al [2006] defined the R33X homozygous nonsense variant in the GJA1 gene in the second case.…”