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Márcia Rodrigues1, Diana Antunes1, Inês Carvalho1, João Freixo1, Marta Amorim1, Teresa Lourenço1, Ana Bernardo2, Luís Nunes1

  1. Especialidade de Genética Médica, Área Departamental de Pediatria Médica, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, EPE
  2. Centro de Diagnóstico Pré-Natal, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, EPE

- XLIV Conferências de Genética Doutor Jacinto Magalhães, 20/02/2015 (poster)

Introduction: Arthrogryposis comprises nonprogressive conditions,  which are characterized by multiple joint contractures. These include a group of autosomal dominant disorders that mainly involve the distal parts of the limbs without a primary neurological and/or muscle disease – the distal arthrogryposis (DA). The various phenotypic forms of DA are designated DA1 through DA10 and present genetic heterogeneity. DA type 2B (DA2B) or Sheldon-Hall Syndrome (SHS, OMIM 601680) is similar to DA1, but affected individuals tend to have typical craniofacial dysmorphisms. DA2B is thought to be the most common of the distal arthrogryposis disorders.
Aims: Provide evidence highlighting the importance of establishing a definitive genetic diagnosis in patients with DA, in order to provide adequate Genetic Counseling (GC) and offer Prenatal Diagnosis (PND) / Preimplantation Genetic Diagnosis (PGD) in future pregnancies.
Clinical Case: A 23-year-old pregnant woman with a personal history of multiple distal contractures suggestive of DA had a fetal ultrasound at 21w+2d of gestational age that revealed increased nuchal translucency, club foot and camptodactyly. Amniocentesis was performed and QF-PCR aneuploidy test and fetal karyotype (46,XX) were both normal. No definitive diagnosis had been established in the pregnant. Because of the potential risk of developmental delay, the couple decided to terminate the pregnancy at 24w. The fetus was observed by an experienced clinical dysmorphologist. By combining the clinical features both of the index case and the fetus, we suspected of DA2B. The molecular testing of TNNI2 gene revealed the heterozygous mutation c.527_529del (p.K175del), confirming the clinical diagnosis of DA2B. After terminating this pregnancy, the patient experienced great psychological distress, with depressive humor and guilt feelings, and she was referred to Psychiatry. GC was offered to the couple and they peremptorily refused PND in future pregnancies, opting for PGD.
Discussion and Conclusion: This clinical case highlights the difficulty that clinicians experience in GC in such cases, when the clinical diagnosis is not yet confirmed by molecular testing. One should always keep in mind that the optimal time for determination of genetic risk and GC regarding prenatal testing is before pregnancy, even when the prognosis is likely good as in DA, as well as address associated psychological aspects.

Palavras Chave: Distal Arthrogryposis, Sheldon-Hall Syndrome, Prenatal Diagnosis, Preimplantation Genetic Diagnosis