Supplemental Digital Content Figure 1:

Photographs of affected males with FG syndrome.

Family 2 (K9367)Family 2 (K9367), III-1He required pureed foods during childhood due to choking. As a child he had frequent pneumonias and otitis media requiring PE tubes. He received developmental interventions from 2 months of age. He engages in repetitive and self-stimulatory behaviors, such as humming, flapping and spinning. He perseverates on phrases and ideas and has compulsive behaviors such as repeatedly flushing a toilet. Family 2 (K9367), II-3Chronic ear infections in the first year of life were treated with gamma globulin. He is well muscled and strong as an adult. He works in his community as a groundskeeper, shoveling snow and splitting wood.

Patient III-1 at age 17 years (left)Patient II-3 at age 43 years (right)

Family 3 (K9411)

Patient IV-2 at age 7 years

Family 3 (K9411), IV-1He was born in 1999 to a 25 year old primigravida. After diminished fetal movements and hypertension in the 3rd trimester, labor was induced at 42 weeks gestation. Birth weight was 3.43 kg (50th percentile) and birth length was 54.6 cm (97th percentile). Patent ductus arteriosus, atrial septic defect (ASD) and a single renal cyst were diagnosed. At 8 days of age when he was discharged, he was still feeding slowly by mouth. At 4 weeks of age, a ventricular septal defect (VSD) was diagnosed. Oral motor issues, poor feeding, mouth breathing and drooling led to occupational therapy from 6 weeks of age. He had laryngeotracheal malacia. Eventually, he fed by mouth. His gastrostomy tube is used for medications only. His oral aversions and restricted food preferences (fruit, bread, macaroni and cheese, yogurt) exacerbate his constipation. With medication, he had 3-4 bowel movements a week. Before he was 3 years of age, he had surgical procedures for occluded tear ducts, ear ventilation tubes and

adenoidectomy. A muscle biopsy showed “mild atrophy.” He had multiple hospital admissions for respiratory difficulties and tracheomalacia. Now he requires treatment with racemic epinephrine with a nebulizer when he has asthma-like symptoms. He had glasses for far-sightedness. He used 2 word phrases and connected speech at 33 months. His speech was nasal. He perseverates on the same topic. Any changes in his routine trouble him. He fixates on certain things that bother him and he is anxious to please people. Eye contact is good and he engages in imaginative play. He is in a regular classroom with extra help for math, reading and speech. He was toilet trained by 6 years of age. The diagnosis of FG syndrome was made when he was 2 1/2 years old. Aside from his affected deceased brother, IV-2, his family history is negative. His only maternal aunt had hyperthyroidism and a healthy son.On physical exam at age 7 ½ years, height was 122.7 cm (25-50th percentile), weight was 19.4 kg (5th percentile) and head circumference was 51 cm (10-25thcentile). There was ridging of the metopic and sagittal sutures, but no plagiocephaly. The eyes were normally spaced with slit-like palpebral fissures and supraorbital puffiness. The simple, low-set, cupped ears were small (4.2 cm, 4.4 cm, <3rd percentile) with narrow external auditory canals. The upper lip was tented and the lower lip was everted. The palate was high and narrow. Teeth were widely spaced in the upper arch and crowded in the lower arch. His sternum was short (10.4 cm, <3rd percentile) and his internipple measurement was narrow (12.2 cm, 10th percentile). He had a harsh midsystolic murmur. His muscle mass was mildly reduced.

Family 3 cont.

Family 4 (K9346)

Patient III-10 at 2 years, 5 years and 16 years. This is the family from the original report of FG syndrome.

Family 5 (K9404)

Patient II-1, at age 3 years, 8 years, 39 years and 61 years.

Patient II-3 at age 26 (These photos are reprinted with permission from The Journal of Pediatrics, Keller MA, Jones KL, Nyhan WL, Francke U, Dixson B. A new syndrome of mental deficiency with craniofacial, limb, and anal abnormalities. J Pediatr. 1976:88(4 Pt. 1);588-591, Copyright 1976, Elsevier).

Family 5 cont.

Patient II-10 at age 16 year and 48 years. (Photo on the left is reprinted with permission from The Journal of Pediatrics, Keller MA, Jones KL, Nyhan WL, Francke U, Dixson B. A new syndrome of mental deficiency with craniofacial, limb, and anal abnormalities. J Pediatr. 1976:88(4 Pt. 1);588-591, Copyright 1976, Elsevier).