Shaheen syndrome is an autosomal recessive form of syndromic intellectual disability. Apart from severe mental retardation, patients suffer from hypohidrosis, hyperkeratosis of the palms and soles, dental enamel hypoplasia and dental caries. Despite the hypohidrosis, patients are seen to have normal numbers of sweat glands. The condition can result in episodic hyperthermia. In some cases, mild microcephaly may develop.
The disorder has an onset at birth. So far, only 3 affected families have been identified, all originating from Saudi Arabia. Due to the limited number of reported cases, information on the condition’s prognosis or prevalence is yet to be ascertained.
The condition is diagnosed based on genetic analysis of the Component of Oligomeric Golgi Complex 6 (COG6) gene. Differential diagnosis includes Congenital Disorder of Glycosylation IIl (CDGIIl), which is also caused by COG6 mutations, and is ruled out by isoelectric focusing studies exhibiting normal transferrin isoform patterns.
The syndrome follows an autosomal recessive pattern of inheritance and is caused by homozygous mutations in the COG6 gene. This gene encodes a subunit of the Conserved Oligomeric Golgi complex, a hetero-octameric peripheral Golgi protein complex believed to play a role in maintaining the structure and function of the Golgi apparatus. Shaheen syndrome is believed to correlate to milder mutations in the COG6 gene such as deep intronic variants, while loss-of-function variants in the gene can cause lethal forms of CDGIIl. The COG6 deep intronic splicing mutation c.1167–24A>G has been implicated in Shaheen syndrome.
Monies et al. (2017) assessed the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One patient, a 1-year-old male, suffered from a failure to thrive, global developmental delay, hiatus hernia, lung hypoplasia, congenital diaphragmatic hernia, low intestinal motility disorder and partial intestinal obstruction. Using a multigene panel for neurological disorders, a homozygous deep intronic mutation (chr13:40273614) was identified in the patient’s COG6 gene, associated with Shaheen Syndrome. Given the atypical presentation of the patient, this case helped in the phenotypic expansion of the disorder.
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