Loeys-Dietz Syndrome
The constellation of pointy nose, high arched palate, bifid uvula, and VSD is characteristic of Loeys-Dietz syndrome, an autosomal dominant connective tissue disorder caused by mutations in TGFBR1 or TGFBR2 genes. 1
Diagnostic Triad
The disease is definitively characterized by three key features 1:
- Arterial tortuosity and aneurysms - most commonly observed in head and neck vessels but can occur throughout the vascular tree
- Hypertelorism (widely spaced eyes)
- Bifid uvula or cleft palate, or a uvula with a wide base or prominent ridge
Associated Cardiac Manifestations
Ventricular septal defects occur as part of the cardiac spectrum in Loeys-Dietz syndrome, along with other congenital heart defects 1:
- Aortic root aneurysms (present in 98% of patients) - the most life-threatening feature
- Atrial septal defects
- Patent ductus arteriosus
- Aortic dissection risk at smaller diameters than other connective tissue disorders
Additional Craniofacial Features
Beyond the diagnostic triad, patients present with 1:
- High arched palate (as described in the question)
- Malar hypoplasia (underdeveloped cheekbones)
- Retrognathia (receding jaw)
- Craniosynostosis
- Blue sclera
Other Systemic Features
- Velvety and translucent skin 1
- Skeletal features similar to Marfan syndrome 1
- Joint laxity 1
- Dural ectasia 1
- Cervical spine abnormalities 1
- Developmental delay 1
Critical Management Implications
The vascular disease in Loeys-Dietz syndrome is particularly aggressive with a mean age of death of 26 years if untreated, making early diagnosis essential 1:
- Aortic repair is recommended at smaller diameters than in other syndromes because aortic dissection occurs at diameters less than 5.0 cm 1
- For young children with severe manifestations, prophylactic surgery is indicated once the aortic diameter exceeds the 99th percentile for age and the aortic valve annulus reaches 1.8 to 2.0 cm 1
- Yearly MR imaging from cerebrovascular circulation to pelvis is required due to the 53% incidence of aneurysms in other vessels 1
Genetic Confirmation
Diagnosis is confirmed through mutational analysis of TGFBR1 or TGFBR2 genes 1. Genetic testing should be pursued immediately when clinical features suggest this diagnosis, as it has profound implications for surgical timing and family screening.
Key Distinguishing Feature from Other Syndromes
Unlike Ehlers-Danlos syndrome vascular type, patients with Loeys-Dietz syndrome are not complicated by tissue fragility, allowing for aggressive surgical management of aneurysms with few complications 1. This is a critical distinction that affects surgical approach and outcomes.