The proband, patient 1, was a 3-day-old female of mixed (Caucasian, African American, and Hispanic) ancestry born via Cesarean section at 35 weeks 5 days gestational age (GA) to a 26-year-old gravida 4 para 2 mother. The pregnancy was complicated by polyhydramnios starting at 21 weeks GA and continuing throughout the pregnancy. At 22 weeks 3 days GA, an intracardiac echogenic focus and nuchal thickening were noted. A subsequent ultrasound at 23 weeks 1 days GA showed the intracardiac echogenic focus and nuchal thickening had resolved but noted a left clubfoot. Another follow-up ultrasound at 28 weeks 6 days was not consistent with left clubfoot.\nAt birth her APGAR scores were 8 and 8 at 1 and 5 min, respectively, but around 5 min, she developed respiratory distress requiring CPAP and admission to the NICU. She was found to have multiple anomalies and dysmorphic features, including cleft palate, flat midface, hypertelorism, creases under the eyes, a small nose with anteverted nares, arachnodactyly of fingers and toes, laterally deviated great toes, and mild pectus carinatum. She was in the 99th percentile for a length of 53.3 cm at birth. She failed her newborn hearing examination in both ears. She remained in the NICU for 6 weeks due to respiratory issues and slowing feeding.\nA karyotype sent at the birth hospital was normal (46, XX). During her NICU stay, a head ultrasound performed 2 days after birth showed mild prominence of the lateral ventricles and no evidence of hemorrhage. A brain MRI performed at 5 weeks of age was overall normal. At 9 weeks of age she was evaluated for bilateral wrist contractures.\nHer family history is significant for a brother and father with similar physical features. Her 17-month-old brother, patient 2, previously presented at 1 day of life with a long neck, excess nuchal skin, large hands and feet with long fingers and toes, and pectus excavatum. He also had a flat midface and a saddle nose. A postnatal chromosome microarray analysis was normal. At the time, the father (patient 3) was found to have similar features including long fingers and toes, pectus excavatum, and laterally deviated great toes (Figure a,b). He also had anteverted nares and mild hypertelorism (Figure c). The father had been in generally good health his entire life. An autosomal dominant disorder was suspected due to the phenotypic similarities between the siblings and their father (Figure ). Given the family history, we decided to offer further genetic testing to determine if there was an underlying hereditary syndrome responsible for their phenotypes.
Patient II:2 was the 65-year-old mother of the twins. She had a history of bilateral congenital cataract extractions. Her fundus examination demonstrated bilateral vitreous syneresis with vitreous membranes. Patient II:3 presented with a cleft palate at an early age. Patients IV:3 and IV:4 presented with a history of retinal detachments but no systemic manifestations. We were not able to collect clinical data from the deceased individuals I:1 and I:2, although historical accounts from II:1 revealed her mother (I:2) had a history of retinal problems.