Absence of Nails, Deaf-mutism, Seizures, and Intellectual Disability: A Case Report

Area of Science:

• Genetics
• Neurology
• Metabolic Disorders

Background:

• Seizures are common in children with intellectual disability, often linked to underlying neural dysfunction.
• DOORS syndrome is an extremely rare genetic disorder affecting the Tricarboxylic Acid (TCA) cycle, with limited reported cases globally since 1961.

Observation:

• An 8-year-old child with global developmental delay, deaf-mutism, and moderate intellectual disability presented with seizures.
• Clinical examination revealed dysmorphic features (anonychia, low-set ears, long philtrum, large lower lip), abnormal dermatoglyphics, and radiological signs of osteodystrophy.
• Despite classical clinical features of DOORS syndrome, genetic analysis did not identify the common TBC1D24 mutation.

Findings:

• The patient was diagnosed with DOORS syndrome, highlighting the condition's rarity and potential for genetic heterogeneity.
• Absence of the typical TBC1D24 mutation in a patient with classic DOORS features suggests alternative genetic causes or variations.
• A four-year follow-up showed seizure pattern changes but no optic atrophy, IQ decline, or peripheral nerve issues.

Implications:

• The findings suggest that DOORS syndrome may exhibit genetic heterogeneity, with potential for varied clinical trajectories based on genetic mutations.
• Children with typical DOORS features and TBC1D24 mutations might experience more progressive deterioration compared to those without.
• Advanced molecular techniques are crucial for identifying novel mutations and understanding unexplained phenotypic expressions in rare genetic disorders like DOORS syndrome.