Patient 2 is a 3-year-old boy, born to second degree consanguineous parents at term by cesarean section, in view of prolonged labor. Birth weight was 2.5 kg (−2 SD). He cried immediately after birth. He is the only child of his parents. Maternal antenatal scan at 6 months of gestation was suggestive of fetal limb deformity that was confirmed after birth. He was referred for evaluation of deformity of bilateral feet, elbows and right knee noted since birth. At birth, he was also found to have cleft palate for which he was operated at 1 year of age.\nAt 6 weeks, his height was 52 cm (−2 SD), OFC 37 cm (−2 SD) and weight 3.3 kg (−2 SD). He had prominent forehead, depressed nasal bridge, long philtrum, telecanthus (Fig. ), and high arched palate. His hair was curly (Fig. ), teeth and nails were normal. Hypermobility of bilateral hip joints was noted along with bilateral dislocated knees, elbows and bilateral clubfeet (Fig. ). He had spatulate thumbs (Fig. ), cylindrical fingers (Fig. ) with short and broad fingertips, and joint laxity. Hearing was normal. There was no evidence of compressive myelopathy. All other examinations were unremarkable. Echocardiography showed normal heart. He achieved head control at 5 months, roll over at 7 months, sitting with support at 10 months, sitting without support at 15 months, crawling at 20 months. He started babbling at 6 months, spoke bisyllables at 15 months and few words with meaning at 20 months.\nRadiograph of skull was unremarkable (Fig. ). Ultrasound of knees at 6 weeks of age suggested absent right patella. Radiographs showed bilateral dislocated elbows (Fig. ), absent right patella (Fig. ), coronal clefts in vertebrae (Fig. ), cervical vertebral kyphosis with subluxation at C4-C5 (Fig. ), and double calcaneum ossification with club feet (Fig. ). Radiographs at 3 months (Fig. and i) and 1 year (Fig. ) suggested delayed carpal ossification. Radiographs at 3 months and 1 year showed thoracolumbar scoliosis (Fig. ) and small capital femoral epiphysis (Fig. ). Thyroid profile was done in view of delayed bone age and was found to be normal. His complete blood counts, serum calcium, serum phosphorous, alkaline phosphatase, and complete urine analysis were normal.
Patient 5 is a 42-year-old man, the second son of unaffected and non-consanguineous parents. He was born, followed by unremarkable pregnancy, at 40 weeks of gestation with a birth weight of 3,580 g (+0.37 SD), length of 52 cm (+0.19 SD) and OFC of 37 cm (+1.92 SD). At birth, he presented with dislocation of knee joints, anterior dislocation of the tibia, bilateral pronounced club feet, and distinct dislocation of both hips. Facial dysmorphism with a flat face and nose, prominent forehead, telecanthus, and myopia was noted (Fig. ). He had broad distal phalanges of the hands (Fig. ), supernumerary carpal bones, and 13 pairs of ribs. During the neonatal period, knee dislocation was treated with manipulation and cast application. Later, club feet were treated with metatarsal osteotomy with posterior soft tissue release. The correction of feet was maintained with feet orthosis until 14 years of age. An arthrodesis of the right knee joint was performed for chronic pain. He later developed a cervical scoliosis with occipito-craniocervical instability. Cervical spine instability was treated with occipitocervical fusion and a return displacement of the soft palate was conducted. No abnormalities of the cardiovascular system were observed. At the age of 37 years, he developed chronic myeloid leukemia. The patient holds a degree in natural science. He is severely limited in his mobility due to the skeletal abnormalities.