Table 1.
Summary of Clinical Features of Individuals with Bi-allelic Loss-of-Function CCDC47 Variants
| Clinical Features | Proband 1 | Proband 2 | Proband 3 | Proband 4 |
|---|---|---|---|---|
| Prenatal and Perinatal History | ||||
| Delivery | C-section | C-section | NSVD | C-section |
| Premature birth | + | term | term | term |
| Polyhydramnios | + | – | – | – |
| Respiratory distress | – | NA | + | + |
| Decreased fetal movements | NA | + | + | NA |
| Bradycardia | + | + | – | + |
| Birth weight (%ile) | 75th | NA | <3rd | 10th |
| Growth Parameters | ||||
| Decreased body weight | + | + | + | + |
| Microcephaly | + | + | + | + |
| Physical Findings | ||||
| Coarse facies | + | + | + | + |
| Midface hypoplasia | + | + | + | – |
| Hypertelorism | + | + | + | – |
| Almond-shaped palpebral fissure | + | + | – | – |
| Epicanthal folds | – | – | + | – |
| Ptosis | + | + | + | + |
| Long eyelashes | + | + | – | – |
| Synophrys | + | – | + | + |
| Ectropion | + | + | – | – |
| Unusual nose | + | + | + | + |
| Downturned mouth | + | + | + | + |
| Macrostomia | – | + | wide mouth | – |
| Macroglossia | – | + | + | + |
| Full or thick lips | + | + | + | + |
| Dental abnormalities | + | – | + | + |
| High arched palate | + | + | + | + |
| Ear abnormalities | + | + | + | + |
| Bilateral otitis media | + | + | + | + |
| Bitemporal narrowing | – | + | + | + |
| Brachycephaly | + | + | + | + |
| Plagiocephaly | + | + | + | – |
| Pruritus | + | + | + | + |
| Unusual hair | + | + | + | + |
| Thoracic hypertrichosis | + | + | + | + |
| Fifth digit hypoplasia and/or clinodactyly | + | + | + | + |
| Dystrophic nails | – | – | + | – |
| Overlapping toes | + | + | + | + |
| Distal arthrogryposis / joint laxity | + | + | + | + |
| Hypoplastic nipples | + | + | + | + |
| Genital anomaly | + | + | – | – |
| Musculoskeletal Findings | ||||
| Hypotonia | + | + | + | + |
| Bilateral hip dislocation | + | + | ND | – |
| Hip dysplasia | + | + | ND | + |
| Bilateral coxa valga | + | – | ND | + |
| Abnormal bone density | + | + | ND | ND |
| Narrow chest | + | + | – | – |
| Fibular bowing | + | + | – | – |
| Genu valgum | – | – | + | – |
| Bilateral clubfoot | + | + | – | + |
| Small feet | + | + | + | + |
| Pectus excavatum | + | – | – | + |
| Scoliosis | – | + | + | – |
| Ocular Findings | ||||
| Hyperopia | + | NA | – | + |
| Astigmatism | + | NA | – | – |
| Cortical visual impairment | + | NA | + | + |
| Immunological Findings | ||||
| Recurrent infections | – | + | + | – |
| Immunodeficiency | – | + | + | – |
| Endocrine Findings | ||||
| Hypothyroidism | – | NA | + | – |
| Rickets | – | + | + | – |
| Respiratory Findings | ||||
| Obstructive sleep apnea | + | + | + | – |
| Central sleep apnea | + | NA | + | – |
| Heart Findings | ||||
| Ventricular septal defect | – | + | – | – |
| Patent ductus arteriosus | + | + | – | – |
| Gastrointestinal Findings | ||||
| Hepatosplenomegaly | + | – | + | – |
| Liver dysfunction | + | ND | + | + |
| Recurrent pancreatitis | + | NA | – | – |
| Exocrine pancreatic insufficiency | + | NA | – | – |
| Gastresophageal reflux | + | NA | + | + |
| Steatorrhea | + | + | – | – |
| Chronic diarrhea | – | + | – | + |
| Gallstones | + | – | – | + |
| Gastrostomy tube | + | – | + | + |
| Elevated bile acids | + | NA | + | + |
| Renal Findings | ||||
| Renal abnormalities | + | + | – | – |
| Neurological Findings | ||||
| Severe global developmental delay | + | + | + | + |
| Hyperreflexia | – | – | + | + |
| Reduced tendon reflexes | + | + | – | – |
| Absent Achilles reflex | + | + | – | – |
| Behavioral issues | – | – | + | + |
| Seizures | – | NA | + | – |
| EEG abnormalities | + | NA | + | + |
| Neuroimaging Findings | ||||
| Abnormal ventricle morphology | + | + | – | + |
| Abnormal corpus callosum | + | – | – | + |
| Cerebral atrophy | + | + | + | + |
| White matter abnormalities | – | – | – | + |
| Cerebellar hypoplasia | – | – | – | + |
Abbreviations: +, present; – absent; C-section, Caesarean section; EEG, electroencephalogram; NA, not available; ND, not done; NSVD, normal spontaneous vaginal delivery.