ß 2008 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:2799–2803 (2008) Clinical Report Tetra-Amelia and Lung Hypo/Aplasia Syndrome: New Case Report and Review Se ´rgio B. Sousa, 1 * Raquel Pina, 2 Lina Ramos, 1 Naigel Pereira, 3 Martin Krahn, 4 Wiktor Borozdin, 5 Ju ¨rgen Kohlhase, 5 Marta Amorim, 1 Katia Gonnet, 4 Nicolas Le ´vy, 4 Isabel M. Carreira, 6 Ana Bela Couceiro, 3 and Jorge M. Saraiva 1 1 Servic ¸o de Gene ´tica Me ´dica, Centro Hospitalar de Coimbra, Coimbra, Portugal 2 Servic ¸o de Anatomia Patolo ´gica, Centro Hospitalar Coimbra, Coimbra, Portugal 3 Centro de Diagno ´stico Pre ´-Natal da Maternidade Bissaya Barreto, Coimbra, Portugal 4 Laboratoire de Ge ´ne ´tique Mole ´culaire, De ´partement de Ge ´ne ´tique Me ´dicale, Ho ˆpital d’enfants La Timone, Marseille, France 5 Center for Human Genetics, Freiburg, Germany 6 Laborato ´rio Citogene ´tica, Instituto Biologia Me ´dica, Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal Received 9 February 2008; Accepted 18 June 2008 Tetra-amelia is a rare malformation that may be associated with other anomalies and is usually inherited in an autosomal recessive pattern. We describe a fetus, born to a non- consanguineous couple, with tetra-amelia, bilateral cleft lip and palate and bilateral lung agenesis, without other anomalies. Karyotype was normal (46,XX) and premature centromere separation was excluded. No mutation was identified upon molecular analysis of WNT3, HS6ST1, and HS6ST3. We reviewed the literature and the differential diagnosis to clarify the clinical delineation of conditions associated with tetra-amelia. The present report describes the sixth family with this pattern of malformations and reinforces the evidence that the ‘‘tetra-amelia and lung hypo/ aplasia syndrome’’ is a distinct autosomal recessive con- dition, with no identified gene thus far. ß 2008 Wiley-Liss, Inc. Key words: tetra-amelia; lung aplasia; cleft lip/palate How to cite this article: Sousa SB, Pina R, Ramos L, Pereira N, Krahn M, Borozdin W, Kohlhase J, Amorim M, Gonnet K, Le ´vy N, Carreira IM, Couceiro AB, Saraiva JM. 2008. Tetra-amelia and lung hypo/aplasia syndrome: New case report and review. Am J Med Genet Part A 146A:2799 – 2803. INTRODUCTION Congenital limb defects have a birth prevalence of 0.55 per 1,000 [Evans et al., 1994]. Amelia, the complete absence of one limb, has a birth prevalence of 0.01 per 1,000 births, in which 50% are syndromic [Evans et al., 1994]. Tetra-amelia, the complete absence of all four limbs, is even rarer, frequently inherited in an autosomal recessive pattern. It is usually described as part of a multiple congenital anomaly syndrome (MIM 273395, 301090 and 273390), associated with craniofacial, pulmonary, central nervous system, heart, skeletal, urogenital malformations, ectodermal dysplasia, and lacrimal duct anomalies. The clinical delineation of the different entities associated with tetra-amelia is complex and the molecular findings are limited. We report an additional patient with tetra-amelia and lung hypo/aplasia syndrome and review the differential diagnosis and clinical delineation of the conditions associated with tetra-amelia. CLINICAL REPORT A 17-year-old healthy woman presented at 20 weeks of gestation in her first pregnancy. There was no known teratogen exposure. The father was a healthy 22-year-old man and there was no consan- guinity or relevant family history. The ultrasonographic evaluation at 20 weeks identified tetra-amelia, bilateral cleft lip and palate, and possible pulmonary hypoplasia. No other anomalies were detected and the amniotic fluid quantity was normal. Pregnancy was terminated at 22 weeks. Clinical examination of the fetus was consistent with the prenatal findings (Fig. 1) and, in addition, micrognathia and low-set ears were *Correspondence to: Dr. Se ´rgio B. Sousa, M.D., Servic ¸o de Gene ´tica Me ´dica, Hospital Pedia ´trico de Coimbra, Av. Bissaya Barreto, 3000-076 Coimbra, Portugal. E-mail: sbsousa@hpc.chc.min-saude.pt Published online 3 October 2008 in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/ajmg.a.32489