Individual IV-15 (Fig. 1) was examined at Gulhane Military Hospital, Ankara, Turkey. He presented at 24-years, was generally healthy, and had not undergone any major surgeries. Details of his birth history are not available. He is the product of a then 29-year-old healthy father and 21-year-old healthy mother who are thought to have a common ancestor, but the precise relationship is not known. He had four limb postaxial polydactyly with bilateral cutaneous syndactyly of toes 2–3. His toenails were dystrophic. Cubitus valgus, pectus deformity, narrow thorax, rhizomelic shortness of the limbs, mild scoliosis, and an S1 spina bifida occulta were also present. Cardiology consultation revealed ASD and VSD of the heart. He married his first cousin and they had two spontaneous abortions, but no information was available on the phenotype of these abortuses.

This 38-year-old male was examined at the NIH Clinical Center and Children's National Medical Center. He is the brother of the proband IV-15 (Fig. 2A). No information is available regarding the pregnancy or birth records. He was born with bilateral postaxial polydactyly of the hands (Fig. 2B) and unilateral postaxial (or central) polydactyly of the right foot (Fig. 2C), and he had poor exercise tolerance throughout childhood. At age 17 years he was diagnosed with an unknown type of septal defect and valvular abnormality. He underwent cardiac surgery at ages 17 and 30 years. The second operation was for replacement of the mitral valve and re-closing the septal defect. A pacemaker was placed after the first operation, but this was removed shortly thereafter as it was infected. The patient claimed that after removal, arrhythmia never recurred. He had a transient episode of aphasia or memory loss, associated with an incorrect adjustment of coagulation therapy and subsequently the symptoms resolved.

He was examined at the NIH Clinical Center in 2007. His weight was 81.4 kg, height was 161.5 cm and head circumference was 57 cm (+ 0.8 SD) (Turkish norm) 4. He had no facial dysmorphic features except for a relatively narrow and tall face and an occipital osteophyte. No extra frenulum or buccal adhesions were present. Hypodontia was evident including maxillary lateral incisors and mandibular first and second molars. No thoracic deformity was noted except scars due to previous operations. He had a bilateral intermediate type of postaxial polydactyly of the hands with a relatively small, but well formed, supernumerary triphalangeal digits. His dermatoglyphic pattern on the left was U,U,U,U,W and on the right was W,U,W,R,R (the sixth digits could not be assessed). He had short, but not hypoplastic, nails on the left hand on the second and third digits, on the right hand of the second digit only (Fig. 2B). Both sixth fingers had a small fingernail and they had normal passive mobility, but active flexion only occurred at the MCP joint. The second fingers of both hands were short with a stubbed or squared tip. His elbows had an increased carrying angle with normal mobility. He had postaxial polydactyly and partial cutaneous syndactyly of toes 4–5 of the right foot (Fig. 2C). He had laterally deviated and broad great toes with thick nails. The left foot was otherwise normal. Radiographs showed (in addition to the external findings above) a coned epiphysis of the left second middle phalanx and prominent styloid processes of the ulnae (Fig. 3A), an irregular notched tip of the distal phalanges of the halluces (Fig. 3B), bowed humeri (Fig. 3C), fusion of the right proximal tibia and fibula (Fig. 3D), and spina bifida occulta of S1. In addition, a pattern profile analysis of the left hand was performed (Fig. 4) 5. Cardiovascular evaluation including echo- and electrocardiography showed mechanical mitral valve replacement and a small membranous VSD and first-degree trifascicular block. Renal ultrasonography showed a solitary 1.8 cm cyst in the right kidney. Mild splenomegaly was also noted. He had mildly elevated hemoglobin levels, suggestive of secondary polycythemia, possibly due to high altitude and obstructive sleep apnea. He had a normal 46,XY male karyotype (resolution between 300–400 bands). See Table 1 for a summary of phenotypic features in this patient and his son.

This 7-1/2-year-old male was also examined at the NIH Clinical Center and Children's National Medical Center. He, the son of IV-9, was the product of a gravida 2, para 2 23-year-old mother. The pregnancy was notable for abnormal fetal movements and poor weight gain. At the seventh month of gestation a fetal ultrasound examination revealed a protuberant anterior chest wall and short limbs, but polydactyly was not detected. After a spontaneous vaginal delivery his birth weight was 3,250 g (10–25^th centile), but his birth length and head circumference are unknown. Four limb polydactyly and a heart murmur were noted at birth. At the age of 6 months he was diagnosed with an atrial and ventricular septal defect and mitral valve insufficiency, which was repaired at age 4 years. At this time his polydactyly was repaired. Generally he was healthy. He is described as successful student in second grade attending regular school. His height was 113 cm, weight 17.4 kg (both 3–10^th centile) (Turkish norms 6) and head circumference 49 cm. (Fig. 5A) Normative head circumference data for this population are disparate: 49 cm is <2^nd centile from one source 7 while this is well within the lower limits of normal, 3^rd – 10^th centile, from a second source 4. Inner canthal distance was 2.5 cm (3^rd – 10^th centile), interpupillary distance was 5.1 cm (~10^th centile) and his outer canthal distance was 7.8 cm (~10^th centile) 4. His nasal tip was broader than his nasal root. Oral examination revealed a single mandibular central incisor. He had two excess mandibular frenula, on each side of the mouth. He also had a central mandibular frenulum. The chest circumference was 53.5 cm (3^rd – 25^th centile) 8. He had a mild lower pectus excavatum and several scars from cardiac surgery. He had a grade 5–6/6 holosystolic murmur. The upper extremities were notable for increased carrying angle, but with normal elbow mobility. Total hand length was 11.8 cm on the left, 12 cm on the right (both <3^rd centile) 8 (Fig. 5B). He had pseudoclubbing of the thumbs bilaterally. He had short, but not hypoplastic, fingernails 1 through 4 bilaterally with a normal fifth fingernail. His digits were proportionately short compared to his hands. Dermatoglyphic pattern on the left was U,U,U,U,W; on the right was U/W,U,U,U,A. He had lateral palm scars from postaxial digit removal. He had partial cutaneous syndactyly of the second and third toes bilaterally and clinodactyly of the second toes with broad toe tips (Figs. 5C,D). All biochemical and hormone blood and urine tests were within the normal range. Dental examination revealed absent maxillary and mandibular lateral incisors. Abdominal, renal and scrotal ultrasounds were normal. Radiographs showed, in addition to the external findings, residual appearance of post-axial polydactyly of hands and prominent cone-shaped epiphyses in the proximal and middle phalanges of all digits (Fig. 6A), atypical shapes of some of the middle and distal phalanges of the feet (Fig. 6B) mild lateral bowing of both humeri (Fig. 6C), spina bifida occulta of S1, and postoperative sternal wires. Pattern profile analysis of the hands was performed (Fig. 4). The bone age was about 6 years and 6 months. Echo- and electrocardiographic evaluation showed a residual cleft mitral valve and mitral regurgitation. He had a normal 46,XY karyotype (resolution 300–400 bands).

The affected family resides in a village of about 1,000 people in Eastern Turkey. Most of the inhabitants of the village claim ancestry from Central Asia and this particular extended family believe their ancestors migrated there from Kyrgyzstan some 150 years ago. The pedigree (Fig. 1) of the family shows that there are consanguineous marriages. The pedigree shows a number of neonatal deaths (e.g., children of III-11 and III-12), reportedly affected with polydactyly of the hands and feet. In addition to the surviving individuals described above, another patient (IV-14) survived to adult age after open-heart operations, but died at age 31 years of cardiac complications. Another nuclear family within the pedigree includes two patients, V-13 and V-14, with a single atrium and bilateral polydactyly of the upper and lower limbs, but without other features of EvC. They died at ages 3 months and 3 years, respectively, because of the heart condition. Another individual in another nuclear family (V-1) had a VSD without any other abnormalities.