Ichthyosis, Spastic Quadriplegia, and Mental Retardation (ISQMR) is an extremely rare neuro-ichthyotic autosomal recessive disorder that is clinically and genetically heterogeneous. It is characterized by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures.
ISQMR occurs due to mutations of the ELOVL4 gene, which codes for a protein called ELOVL Fatty Acid Elongase 4. The protein encoded by this gene plays a role in adding carbon molecules to long-chain and very-long chain fatty acids.
This disorder is usually inherited in an autosomal recessive manner.
Aldahmesh et al. (2011) reported on a Saudi Arabian individual with recessive ELOVL4 mutations who displayed congenital ichthyosis. The patient was born to healthy consanguineous first-cousin parents. He was noted to have a collodion membrane covering the skin at birth, which resolved to be replaced with dry ichthyotic skin affecting all regions of the body. He showed profound developmental delay and was severely handicapped with little interest in his surroundings when examined at age 6 years. At age 4 months, he developed frequent refractory seizures. He also had severe hypertonia in the upper and lower extremities and was generally immobile, consistent with spastic quadriplegia. Brain MRI showed severely delayed myelination and brain atrophy. Other features included recurrent bronchial asthmatic attacks, bilateral inguinal hernias, small testicular size, and loss of most of his teeth. There were no clear dysmorphic features. Biochemical analysis of fibroblast fatty aldehyde dehydrogenase (FALDH) activity was found to be normal in the first case, which suggested that this index had ‘‘pseudo-SLS’’. Exome sequencing revealed ahomozygouse truncating nonsense mutation in exon 5 of ELOVL4 as the most plausible candidate for causing the disease phenotype.
Monies et al. (2017) portrayed the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One male patient suffered from contractures, ichthyosis, failure to thrive, microcephaly, fine/gross motor delay, speech delay, spasticity, seizures, optic atrophy and Sjogren Larsson syndrome. He was born premature at 34 weeks to a consanguineous family and reported a positive family history. Whole exome sequencing helped identify a homozygous mutation (c.575A>G, p.H192R) in exon 5 of the patient’s ELOVL4 gene, associated with ISQMR. As the ELOVL4 gene had previously been tentatively linked to ISQMR, this report helped confirm its association with the disorder.
To contribute with your findings to the content of this record, please fill the CTGA Database Information Submission Form and email it, along with supportive documents, to email@example.com.