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 6 is a 39-year-old woman, born to non-consanguineous parents. Normal vaginal delivery took place at full term. Birth measurements were in the normal range. Her parents, sister and brother were unaffected, similar to her first son. Her second son was affected (see patient 7). Congenital club feet were treated with tenotomy of Achilles tendon. Bilateral hip dislocation was treated with several orthopedic surgeries. In early childhood, she could walk with braces. She still had club feet deformity. At the age of 29, she became wheelchair-dependent due to hip dislocation and club feet.\nAt the age of 39 years, physical examination revealed height of 145 cm (−3.5 SD), OFC of 57 cm (−1.8 SD), and weight of 85 kg (+1.8 SD). She had prominent forehead, depressed nasal bridge, long philtrum, and telecanthus (Fig. ). She had bilateral dislocated elbows (Fig. ) and cylindrical fingers with short and broad fingertips and spatulate thumbs (Fig. ). She had bilateral fixed clubfeet deformities with partial syndactyly of toes 2/3 on the right (Fig. ). Wrist joints were normal and there was no pectus deformity. Teeth and nails were normal. Hearing was normal. Numbness of the upper extremities was suggestive of compressive myelopathy. Radiographs confirmed bilateral dislocated elbows (Fig. ), hip dislocation with ossified right hip joint (Fig. ), and deformities of cervical vertebral bodies (Fig. ).