Oculo-facio-cardio-dental (OFCD) syndrome: four cases in two Japanese families

Abstract

Purpose : Oculo-facio-cardio-dental (OFCD) syndrome is an extremely rare X-linked dominant disorder that is lethal in men. It is associated with congenital cataract, microphthalmia, and systemic complications including facial dysmorphic features, congenital heart disease, and tooth abnormalities. OFCD syndrome is caused by variants in BCOR. We performed a retrospective observational clinical study to assess the long-term clinical course of Japanese OFCD patients with BCOR variants.

Methods : We clinically examined and collected blood samples from four OFCD patients from two families who had been visiting our hospitals for a long time. To identify the causative variants, whole-exome sequencing (WES) was performed to identify the candidate variants, which were confirmed by Sanger sequencing.

Results : Case 1: A 12-year-old girl with a sporadic case, had congenital cataracts and microphthalmia immediately after birth. At 2 months of age, a lensectomy was performed on both eyes. Subsequently, she developed secondary glaucoma and was treated surgically several times; this included a tube shunt surgery in her right eye. She also had a broad nasal bridge, an atrial septal defect (which was surgically treated), and teeth dysplasia (radiculomegalies with prolonged dental roots). She had a de novo nonsense variant [c.4438C>T:p.(Arg1480*)] in BCOR.
Cases 2–4: A 16-year-old girl, a 46-year-old mother, and a 73-year-old grandmother, had congenital cataracts and microphthalmias. The girl underwent lensectomy in the right eye, and the grandmother had pseudophakia in her left eye. Nystagmus was observed in each patient. All patients had broad nasal bridges and elongated faces. The youngest had a heart murmur when she was a toddler. The girl had a cleft palate and the mother had teeth dysplasia. The girl and the mother had a toe malformation. They had a novel frameshift variant [c.717_729del:p.(Asn240Phefs*22)].

Conclusions : We reported the clinical features of four Japanese OFCD syndrome patients with BCOR variants. WES was useful for a precise diagnosis. Congenital cataracts and microphthalmia were common in all cases. Facial, cardiac, and dental abnormalities varied in severity. In some cases, skeletal abnormalities were observed. It is vital to obtain additional information on Japanese OFCD syndrome patients. The data from this study provides further insight into OFCD syndrome and may be useful for formulating an accurate diagnosis.

This is a 2021 ARVO Annual Meeting abstract.