Neonatal presentation of Loeys-Dietz syndrome: two case reports and review of the literature

Ital J Pediatr. 2022 Jun 6;48(1):85. doi: 10.1186/s13052-022-01281-y.


Background: Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardiovascular manifestations, especially aortic dilatations and arterial tortuosity, craniofacial and skeletal features, joint laxity or contractures, skin abnormalities, hypotonia and motor delay. Its diagnosis is established by the identification of a pathogenic variant in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 or TGFB3 genes. In newborns and toddlers, vascular complications such as aneurism rupture, aortic dissection, and intracerebral incidents, can occur already in the weeks of life. To avoid these events, it is crucial to precociously identify this condition and to start an apunderwent a surgical procedurepropriate treatment which, depending on the severity of the vascular involvement, might be medical or surgical.

Case presentation: We report two cases of Loeys-Dietz syndrome precociously diagnosed. The first describes a male, born at 38 + 1 weeks of gestation, with hypotonia, joint hypermobility, arachnodactyly, and fingers joint contractures, as well as senile appearance and facial dysmorphisms. In the suspect of a connective tissue disorder, an echocardiography was performed and revealed an aortic root dilatation of 13 mm (Z score + 3). A trio based Whole Exome Sequencing found a novel de novo variant in the TGFBR2 gene. Despite the onset of a low-dose angiotensin receptor blocker therapy, the aneurysm progressed. The second case describes a female, born at 41 + 3 weeks of gestation. During the neonatal examination a cleft palate was noticed, as well as minor dysmorphisms. Since the family history was suspicious for connective tissue disorders, a genetic panel was performed and identified a pathogenetic variant in TGFB3 gene. In this case, the echocardiography revealed no abnormalities.

Conclusions: In addition to our cases, we identified 14 subjects with neonatal LDS in the medical literature. All of them had aortic involvement. Skeletal and face abnormalities, including eyes and palate malformations, were also highly frequent. Overall, 10 subjects required medical therapy to avoid aneurysm progression, and 8 patients underwent surgical procedures. Benefits of an early diagnosis of LDS are various and imply a potential modification of the natural history of the disease with early interventions on its complications.

Keywords: Aneurysm; Connective tissue disorder; Loeys-Dietz syndrome; Newborn.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Connective Tissue Diseases* / complications
  • Contracture* / complications
  • Female
  • Humans
  • Infant, Newborn
  • Loeys-Dietz Syndrome* / complications
  • Loeys-Dietz Syndrome* / diagnosis
  • Loeys-Dietz Syndrome* / genetics
  • Male
  • Muscle Hypotonia / complications
  • Receptor, Transforming Growth Factor-beta Type II / genetics
  • Transforming Growth Factor beta3


  • Transforming Growth Factor beta3
  • Receptor, Transforming Growth Factor-beta Type II