RIN2 syndrome: Expanding the clinical phenotype

Area of Science:

• Genetics
• Molecular Biology
• Rare Diseases

Background:

• Biallelic defects in the RIN2 gene cause a rare autosomal recessive connective tissue disorder, previously termed MACS syndrome or RIN2 syndrome.
• The condition is characterized by macrocephaly, alopecia, cutis laxa, scoliosis, dysmorphic facial features, and progressive facial coarsening.
• Phenotypic overlap exists with Ehlers-Danlos syndromes (EDS), particularly dermatosparaxis and kyphoscoliosis subtypes.

Observation:

• A 10th patient, the first of Caucasian origin and oldest reported, with homozygous RIN2 mutation c.1878dupC (p. (Ile627Hisfs*7)) is described.
• This patient presented with hallmark features of RIN2 syndrome.
• Additionally, novel symptoms including cervical vertebral fusion, mild hearing loss, and colonic fibrosis were observed.

Findings:

• The study details the clinical findings of all reported patients with RIN2 mutations.
• It provides an overview of the expanded clinical phenotype of RIN2 syndrome.
• Possible pathogenic mechanisms underlying the condition are summarized.

Implications:

• This case expands the known clinical spectrum of RIN2 syndrome, including previously unassociated symptoms.
• Understanding these mechanisms can aid in diagnosing and managing patients with this rare connective tissue disorder.
• Further research into RIN2 gene function and its role in connective tissue development is warranted.