Marfan syndrome with neonatal progeroid syndrome-like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1-gene

• Published in: American journal of medical genetics. Part A Vol. 152A; no. 11; pp. 2749 - 2755
• Main Authors: Graul-Neumann, Luitgard M., Kienitz, Tina, Robinson, Peter N., Baasanjav, Sevjidmaa, Karow, Benjamin, Gillessen-Kaesbach, Gabriele, Fahsold, Raimund, Schmidt, Hartmut, Hoffmann, Katrin, Passarge, Eberhard
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2010; Wiley-Liss
• Subjects: Adolescent; Adult; Biological and medical sciences; Body Fat Distribution; Child; Child, Preschool; Dermatology; Electric Impedance; FBN1 mutation; Female; Fibrillin-1; Fibrillins; Frameshift Mutation - genetics; Humans; Infant, Newborn; lipodystrophy; Lipodystrophy - complications; Lipodystrophy - genetics; Magnetic Resonance Imaging; Marfan syndrome; Marfan Syndrome - complications; Marfan Syndrome - genetics; Marfan Syndrome - physiopathology; Medical genetics; Medical sciences; Microfilament Proteins - genetics; neonatal progeroid syndrome; Pregnancy; Progeria - complications; Progeria - genetics; Protein-Serine-Threonine Kinases - genetics; Receptors, Transforming Growth Factor beta - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin involvement in other diseases. Miscellaneous. General aspects; Young Adult; Connective tissue disease; Skin disease; Elastic tissue disease; Wiedemann Rautenstrauch syndrome; Frameshift mutation; FBN1 mutation; Marfan syndrome; Genetic disease; neonatal progeroid syndrome; Gene; Systemic disease; Genetics; Lipodystrophy; Adipose tissue disorders
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.33690

We report on a 25‐year‐old woman with pronounced generalized lipodystrophy and a progeroid aspect since birth, who also had Marfan syndrome (MFS; fulfilling the Ghent criteria) with mild skeletal features, dilated aortic bulb, dural ectasia, bilateral subluxation of the lens, and severe myopia in addition to the severe generalized lipodystrophy. She lacked insulin resistance, hypertriglyceridemia, hepatic steatosis, and diabetes. Mutation analysis in the gene encoding fibrillin 1 (FBN1) revealed a novel de novo heterozygous deletion, c.8155_8156del2 in exon 64. The severe generalized lipodystrophy in this patient with progeroid features has not previously been described in other patients with MFS and FBN1 mutations. We did not find a mutation in genes known to be associated with congenital lipodystrophy (APGAT2, BSCL2, CAV1, PTRF‐CAVIN, PPARG, LMNB2) or with Hutchinson–Gilford progeria (ZMPSTE24, LMNA/C). Other progeria syndromes were considered unlikely because premature greying, hypogonadism, and scleroderma‐like skin disease were not present. Our patient shows striking similarity to two patients who have been published in this journal by O'Neill et al. [O'Neill et al. (2007); Am J Med Genet Part A 143A:1421–1430] with the diagnosis of neonatal progeroid syndrome (NPS). This condition also known as Wiedemann–Rautenstrauch syndrome is a rare disorder characterized by accelerated aging and lipodystrophy from birth, poor postnatal weight gain, and characteristic facial features. The course is usually progressive with early lethality. However this entity seems heterogeneous. We suggest that our patient and the two similar cases described before represent a new entity, a subgroup of MFS with overlapping features to NPS syndrome. © 2010 Wiley‐Liss, Inc.