ATM Gene Mutation in Ataxia Telangiectasia
This patient most likely has a mutation in the ATM gene, as the clinical presentation of progressive cerebellar ataxia beginning in early childhood, oculomotor apraxia (eyes darting past targets), and prominent telangiectasias on the conjunctivae and face is pathognomonic for ataxia telangiectasia (A-T). 1
Clinical Reasoning
The constellation of findings in this 3-year-old boy creates a highly specific diagnostic pattern:
Progressive Neurologic Deterioration
- Progressive cerebellar ataxia developing between ages 1-4 years is the hallmark neurologic feature of A-T, with this patient showing typical onset after initially normal motor development at 12 months 1
- Oculomotor apraxia (eyes darting past visual targets) is a characteristic finding in A-T that distinguishes it from other ataxias 1
- The progressive, uncoordinated gait without other focal deficits points specifically to cerebellar pathology rather than other neurodegenerative processes 1
Pathognomonic Vascular Findings
- Conjunctival and facial telangiectasias are distinctive vascular malformations that occur specifically in A-T due to ATM protein dysfunction dysregulating angiogenesis 2
- These telangiectasias typically appear between ages 3-6 years and are directly related to the absence or reduced function of ATM protein 2
Genetic Basis
- A-T is caused by biallelic pathogenic variants in the ATM gene (autosomal recessive inheritance), which encodes a phosphatidylinositol-3 kinase family protein critical for DNA damage response and cell cycle regulation 1
- The ATM gene is located on chromosome 11q22-23, contains 66 exons, and encodes a 350 kDa protein 3
- Pathogenic variants typically result in absent or dysfunctional ATM protein, preventing proper cellular response to DNA damage 1
Why Not the Other Options
GNAQ mutations cause Sturge-Weber syndrome with port-wine stains and seizures, not progressive ataxia with oculomotor apraxia [@general medical knowledge]
NF2 mutations cause neurofibromatosis type 2 with bilateral vestibular schwannomas and other CNS tumors, not the specific combination of cerebellar ataxia and telangiectasias [@general medical knowledge]
TSC1 mutations cause tuberous sclerosis with seizures, intellectual disability, and hamartomas, not progressive ataxia with oculomotor findings [@general medical knowledge]
VHL mutations cause von Hippel-Lindau disease with retinal and CNS hemangioblastomas and renal cell carcinoma, not cerebellar ataxia with telangiectasias [@general medical knowledge]
Critical Management Implications
Immediate Diagnostic Confirmation
- Obtain ATM gene sequencing (including deletion/duplication analysis) to confirm the diagnosis 1
- Check serum alpha-fetoprotein (AFP) levels, which are characteristically elevated in A-T 1
- Perform chromosome breakage analysis to demonstrate increased radiosensitivity 1
- Assess immunoglobulin levels (IgA, IgE, IgG2) as immunodeficiency is common 1
Multidisciplinary Referrals Required
- Neurology for progressive cerebellar ataxia and oculomotor apraxia management 1
- Immunology/hematology for immunodeficiency management and cancer surveillance, as up to 40% develop malignancy (typically non-Hodgkin lymphoma or acute lymphoid leukemia) 1
- Pulmonology for recurrent infections and restrictive lung disease monitoring 1
- Gastroenterology for swallowing evaluation and nutritional support 1
- Oncology for cancer risk assessment and surveillance 1
Critical Pitfall to Avoid
- Never use ionizing radiation (X-rays, CT scans) for routine imaging in patients with A-T, as they have extreme cellular and clinical radiosensitivity due to defective DNA damage response 1
- Use MRI instead for any necessary imaging studies 1