ß 2008 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:3198–3201 (2008) Clinical Report Developmental Delay, Dysmorphic Features, Neonatal Spontaneous Fractures, Wrinkled Skin, and Hepatic Failure: A New Metabolic Syndrome? Andre ´ Me ´garbane ´, 1,4 * Leila Samaras, 1 Rima Che ´did, 1 Eliane Chouery, 1 Dominique Chre ´tien, 2 Catherine Caillaud, 3 Joelle Abou-Ghoch, 1 and Nadine Jalkh 1 1 Unite ´ de Ge ´ne ´tique Me ´dicale, Faculte ´ de Me ´decine, Universite ´ Saint Joseph, Beirut, Lebanon 2 Inserm U781 and Department of Genetics, Ho ˆpital Necker-Enfants Malades, Universite ´ Rene ´ Descartes Paris V, Paris, France 3 INSERM, U567, Universite ´ Paris Descartes, CNRS (UMR 8104), Paris, France 4 Institut Je ´ro ˆme Lejeune, Paris, France Received 17 January 2007; Accepted 21 August 2008 We report on a consanguineous Lebanese family where two sibs had an axial hypotonia, developmental delay, hirsutism, large fontanels with delayed closure, and dysmorphic facial features that consist of frontal bossing, prominent eyes, slightly down-slanting palpebral fissures, hypertelorism, telecanthus, long eyelashes, gum hypertrophy, and pointed chin. In addition, they had short neck, abnormal thoracic configuration, wrinkled skin on the hands and abdomen, hepato-splenomegaly and neonatal spontaneous fractures. Their overall health and hepatic function deteriorated every time they had fever. The eldest boy died at the age of 18 months secondary to a hepatic failure. Laboratory exams did not reveal any anomaly except for the hepatic function. Differential diagnoses are discussed and the possibility that we might be reporting on a new metabolic syndrome is raised. ß 2008 Wiley-Liss, Inc. Key words: malformations; consanguinity; liver; bones; skin How to cite this article: Me ´garbane ´ A, Samaras L, Che ´did R, Chouery E, Chre ´tien D, Caillaud C, Abou-Ghoch J, Jalkh N. 2008. Developmental delay, dysmorphic features, neonatal spontaneous fractures, wrinkled skin, and hepatic failure: A new metabolic syndrome? Am J Med Genet Part A 146A:3198 – 3201. INTRODUCTION This is a report on Lebanese sibs, offspring of consanguineous parents, presenting with a unique pattern of abnormalities consisting of an axial hypo- tonia, developmental delay, dysmorphic facial fea- tures, short neck, wrinkled skin, abnormal thoracic configuration, hepato-splenomegaly, liver dysfunc- tion and neonatal spontaneous fractures. The nosol- ogy suggests the presence of a hitherto unreported syndrome. CLINICAL REPORT Patient 1 The propositus, a boy, was the first child of a healthy P1G1A0 Lebanese woman. The parents are consanguineous. His pregnancy was normal. No known toxic or medical exposures or unusual events were reported during the gestation. There was no history of birth defects, or increased miscarriage rate in relatives. Delivery was at term by spontaneous vaginal delivery. At that time, the mother was 26 years old and the father 32. The baby boy’s birth weight was 3,150 g (35th centile), length 50 cm (50th centile), and head circumference (OFC) 34 cm (10th centile). Spontaneous fractures of the left arm and of the right clavicle were detected after a routine examination and confirmed by X-rays (Fig. 1). Other complaints were poor overall health and deterioration of liver enzymes every time he got sick. This boy was first evaluated by us at age 12 months. His weight was 9,700 g (50th centile), length 79 cm (75th centile), and OFC 47 cm (50th centile). Grant sponsor: Association Franc ¸aise contre la Myopathie (AFM). *Correspondence to: Andre ´ Me ´garbane ´, M.D., Ph.D., Unite ´ de Ge ´ne ´tique Me ´dicale, Faculte ´ de Me ´decine, Universite ´ Saint Joseph de Beyrouth, 42, rue de Grenelle, 75007 Paris, France. E-mail: megarbane@usj.edu.lb Published online 14 November 2008 in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/ajmg.a.32579