Jornal de doenças genéticas e relatórios genéticos

Challenging Reproductive Genetic Counseling in Families at High Risk for Rare Genetic Syndromes – A Case Report with Possible Denys-Drash Syndrome

Hachmeriyan M, Andonova S, Levkova M, Stoyanova M, Kalchev K, Vasilev P, Miteva V, Tsvetkova M, Bradinova I and Angelova L

Calculating the recurrence risk is an integral part of everyday practice of the genetic counselor, but certain difficulties occur when explaining it to the parents of a child with a rare dysmorphic syndrome.

We present a case of a family with first newborn with multiple anomalies and exitus letalis, registered on the second day. At birth, the baby presented with limb malformations. Additionally, a spontaneous pneumothorax, neonatal cerebral ischemia, and intraamniotic infection were diagnosed. A post-mortem examination revealed additional multiple internal malformations such as patent foramen ovale, bicornuate uterus, accessory spleen, bilateral adrenal hyperplasia, unilateral Wilm’s tumor of the left kidney, diffuse glomerular and interstitial fibrosis, and protein cylinders in dilated renal tubules.

Standard GTG banding karyotyping showed a normal male karyotype 46,XY,16qh+ that did not correspond to the female phenotype of the patient’s genitalia. Postmortem findings together with sex phenotype/genotype discordance suggested Denys-Drash syndrome as possible diagnosis. Amplification of all exons but exon 9 of WT1 gene was not successful on DNA extracted from formalin-fixed paraffin-embedded tissue (FFPET) sample. Sanger sequencing of exon 9 did not reveal a causative mutation. In current case the severe neonatal presentation and absence of molecular conformation complicated giving a certain prognosis for the recurrence risk. Reproductive genetic counseling in families with rare genetic conditions could be very challenging.