OMIM ID:
Orofaciodigital Syndrome, Type VI
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Hypertelorism and epicanthal folds have been described. Some patients have nystagmus and strabismus. Ocular apraxia and difficulties in smooth visual pursuit may be present.
Systemic Features
Polydactyly of the hands is a common feature. The central metacarpal is often Y-shaped leading to ‘central polydactyly’. The large toes may be bifid. Cognitive deficits are common and some patients have been considered mentally retarded. The ears are low-set and rotated posteriorly. Some patients have a conductive hearing loss. Oral anomalies may include a lobed tongue, lingual and sublingual hemartomas, micrognathia, clefting, and multiple buccoalveolar frenula. Congenital heart anomalies, micropenis, and cryptorchidism have been reported. Tachypnea and tachycardia have been noted. Some patients have some degree of skeletal dysplasia and many individuals are short in stature.
The presence of cerebellar abnormalities such as hypoplasia (including absence) of the vermis may help to distinguish type VI from other forms of OFDS. Hypothalamic dysfunction may be responsible for poor temperature regulation (hyperthermia). The ‘molar tooth sign’ seen on brain MRIs in Joubert syndrome (213300) is also present in OFDS VI.
Genetics
Inheritance
This is a rare condition with limited family information. Parents in one family were consanguineous, and multiple affected sibs in other families suggest this may be an autosomal recessive condition. Homozygous mutations in TMEM216 have been found. Other patients have mutations in C5orf42.
Many of the clinical features in OFDS VI are also found among individuals with Joubert (213300) and Meckel (249000) syndromes that also sometimes have mutations in the TMEM216 and C5orf42 genes. Some consider all of these conditions to be members of a group of overlapping disorders called ciliopathies or ciliary dyskinesias.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.