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A very rare congenital genetic neurological disorder characterized by agenesis/hypoplasia of corpus callosum with developmental abnormalities, ocular disorders, and variable craniofacial and skeletal abnormalities.
ORPHA:1777Classification level: Disorder
The syndrome is a rare and has been reported in more than 7 families to date, representing 56 affected individuals. While generally considered a rare disease, one large cohort of Arab patients (1000 individuals) suggested that start codon mutations in C12ORF57 alone accounts for 1.5% of all cases of intellectual disability, a contribution that rivals that of the much more familiar Fragile‐X syndrome and would make it the single most common cause of recessive intellectual disability/developmental delay in Saudi Arabia. Most affected families are of Middle-Eastern Arab descent, specifically Saudi Arabian. Most reported families have multiplex cases of Temtamy syndrome and almost all are from consanguineous unions. Male and female patients have been reported.
.Age of onset is generally in the neonatal period and in infancy. The manifestations of Temtamy syndrome are variable. The main clinical findings are dysmorphic facies (including elongated face, hypertelorism, prominent nose, low-set ears, and micrognathia), hypotonia, moderate to severe intellectual disability, intractable seizures and autistic features such as absent language or stereotypy. Motor and cognitive delay usually manifests in early childhood. Skeletal anomalies may include brachydactyly of the hands and feet, genu vara, and pes planus. Visual abnormalities include microphthalmia, coloboma of iris, esotropia, and optic atrophy, sometimes leading to progressive loss of vision. Atrial septal defect was also found in some patients. Involvement of other systems was not reported.
The pathogenesis of Temtamy syndrome is not known. Various mutations (homozygous, missense, compound heterozygous) in the C12ORF57 gene (12p13.31) have been reported in affected patients. The gene is of unknown function but appears to be required for development of the corpus callosum and the eye. It is expressed primarily in the neurological, visual, and cardiovascular systems. In vitro cellular expression studies indicated that the mutation decreased protein synthesis suggesting the lost-of-function mechanism and phenotypic variability.
Diagnosis is based on the specific constellation of clinical signs and brain imaging. Brain magnetic resonance imaging (MRI) of affected patients has shown aplasia, thickening, or hypoplasia of the corpus callosum, thalamic hypoplasia, and rarely colpocephaly.
Differential diagnoses include muscle-eye-brain disease, Peters-plus, Walker-Warburg, Aicardi, Donnai-Barrow, and Baraitser-Winter syndromes.
Temtamy syndrome follows an autosomal recessive pattern of inheritance. Genetic counseling should be offered to affected families.
Management and treatment
Currently, management of the disease is symptomatic.
Prognosis and quality of life depend on the severity of disease manifestations.