Balkan Journal of Medical Genetics

MISDIAGNOSIS OF TRACHER-COLLINS SYNDROME INITIALLY ATTRIBUTED TO DRUG TERATOGENICITY: A MOROCCAN CASE REPORT
Lamzouri A, EL Rherbi A, Ratbi I, Laarabi FZ, Chahboune R, Elalaoui SC, Hamdaoui H, Bencheikh RS, Sefiani
*Corresponding Author: Afaf Lamzouri (MD, Ass. Prof.): Department of Medical Genetics and Oncogenetics, Mohammed VI University Hospital, Faculty of Medicine and Pharmacy of Tangier, BP 365 km 15 Gzenaya Tangier, Morocco. Fax: 05.39.39.21.46. Phone number: 00 212 6 10 77 79 59. Email: lamzouriafaf@hotmail.com / lamzouriafaf82@gmail.com / a.lamzouri@uae.ac.ma
page: 69

CASE PRESENTATION

The patient is a 7-year-old male, first child of Moroc- can consanguineous parents (first-degree), aged of 29-year- old for the mother and 37-year-old for the father. Preg- nancy and delivery were normal, and the child was born at term with normal physical measurements. The mother had no history of abdominal trauma or radiographic examina- tion, but she had been taking an antidepressant treatment based on trimipramine Surmontil ® during the first two months of pregnancy. The child had normal psychomotor development and has been schooled with good follow-up. Upon general examination at 7 years, the patient’s body weight was 23 Kg (50th percentile), head circum- ference 45 cm (50th percentile), and height 123 cm (70th percentile). He was dysmorphic with coloboma of the lower eyelids, downslanting palpebral fissures, missing eyelashes, and bilateral symmetrical hypoplasia of the zygomatic bones (Fig. 1). The rest of his physical examina- tion was normal; in particular, he has no ear abnormalities. Ophthalmological examination revealed a corneal ulcer with palpebral coloboma, otorhinolaryngol-scopic and dental examinations were normal. From the very first months of their child’s life, the parents keenly observed facial dysmorphia. Upon seek- ing medical advice, the consulting pediatrician attributed this dysmorphia to the antidepressant treatment that the mother had undergone during her pregnancy. At that time, neither a genetic consultation nor a pharmacovigilance assessment was sought. The attribution of the child’s condition to the mother’s medication has precipitated profoundly distressing psycho- logical and social consequences. This includes a deteriora- tion in the mother’s depressive syndrome, characterized by self-blame, self-indignation, and a substantial decline in her self-esteem. Adding to her distress, the child’s father has consistently expressed a threat of divorce, associat- ing the mother with misfortune, even extending to their own child. It was not until the child reached the age of seven that the mother, realizing the existence of a national pharmacovigilance center, made the decision to formally report her child’s case. Her primary motivation was to share her personal ordeal and to raise awareness about the potential risks associated with the medication. Upon receiving the case report, the physician con- ducted a causality assessment using the French method of imputability study [2]. To establish a comprehensive semi- otic score and eliminate potential differential diagnoses, a genetic consultation was deemed necessary. Consequently, a genetic consultation was sought, ultimately leading to the accurate rectification of the etiological diagnosis of dysmorphia. According to the French method for assessing the causality of adverse drug reactions, the pharmacologist assigned a level of doubt regarding the drug’s origin, as indicated by an Intrinsec Score of I2. The chronological score was noted as C2, and the semiological score as S1. The extrinsic score, designated as B1, was based on the available data for trimipramine, which although limited, appeared to suggest the absence of a specific malforma- tion risk associated with trimipramine antidepressants [3]. During the parental evaluation, it was observed that the father exhibited discreet coloboma and mild hypoplasia of the zygomatic bones. Treacher Collins syndrome was considered a potential diagnosis due to the presence of characteristic dysmorphic features and a family history consistent with autosomal dominant inheritance. Prior to conducting genetic studies, informed consent was obtained from the proband’s parents. The genetic testing conducted involved a multigene panel, including genes TCOF1, POLR1B, POLR1C, and POLR1D. The results revealed a heterozygous frameshift mutation NM_001371623.1(TCOF1): c.4372_4376del (p.Lys1458fs) in exon 24 of the TCOF1 gene for the pro- band. However, the father declined to participate in the genetic study, as he was unwilling to accept that he could be the carrier of the disease.

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