Multiple Facial Milia in Patients With Loeys-Dietz Syndrome

Abstract

Background: Loeys-Dietz syndrome (LDS) results from mutations in the TGFBR1 or TGFBR2 genes and is known to cause aggressive cardiovascular disease, including aortic aneurysms and dissections at an early age. Currently, craniofacial, skeletal, and cardiovascular findings play an important role in early recognition of the disease. While many patients do have recognizable cutaneous features of LDS, little information about associated skin findings has been reported. Observations: Four unrelated patients with LDS due to a mutation in the TGFBR2 gene were observed to have numerous facial milia. All 4 patients reported that the milia had been present since early childhood and had increased in number with time. In some cases, affected relatives were reported to have similar findings. Conclusions: To our knowledge, the association of LDS and facial milia has not been previously reported. Recognition of LDS is important because the aggressive aortic and arterial disease warrants early surgical therapy. Facial milia and other cutaneous findings may possibly differentiate LDS from Marfan syndrome and other related disorders, thereby facilitating early diagnosis. Interestingly, each of the 4 patients with LDS and facial milia had a mutation in TGFBR2 despite widespread variability in other features of the disease.

Genotypic Categorization of Loeys-Dietz Syndrome Based on 24 Novel Families and Literature Data

“…Hernias were of different types (diaphragmatic, inguinal, or umbilical) and together with joint laxity were registered in half of patients. Cutaneous findings appeared extremely frequent including translucent skin, easy bruising and striae; together with facial milia, described in half mutated patients, skin features appeared as extremely useful handle for diagnosis [14]. Overall, our data confirm broad overlap between LDS phenotypes caused by TGFBR1/2 pathogenic variants, as previously assessed [6].…”

Hand and fibrillin‐1 deposition abnormalities in Loeys–Dietz syndrome—expanding the clinical spectrum

“…In addition, our proband presented with prenatally detected skeletal abnormalities; including club feet and hand abnormalities. He also demonstrated multiple facial milia and respiratory distress that have been reported as early signs of LDS [Lloyd et al, ; Kuppler et al, ]. While the club foot/feet and hand contractures were previously described in 23% and 13% of a group of 65 LDS patients, respectively [Erkula et al, ], the syndactyly and absent distal phalanges has not been previously reported in conjunction with LDS.…”

Atrophoderma Vermiculatum

“…2 The second, 24-year-old patient, was included in a study of 25 patients with LDS. 3 She had multiple facial milia around the eyes and malar AV. A mutation in TGFBR2 was identified.…”

“…Of additional interest, 3 other patients in that same study also had facial milia and a TGFBR2 mutation. 3 Therefore, milia may be a feature of TGFBR2-related LDS.…”

“…It is typically seen in men older than 40 years. [2][3][4][5] Report of a Case | A 57-year-old man sought medical attention for dysphagia, chest pain, and a 40-lb weight loss over 6 months. Imaging demonstrated a distal esophageal ulcerating mass covering 50% to 75% of the esophageal circumference.…”