Table 1 Comparison of the clinical features between the siblings with the homozygous synonymous FAM111A variant and patients with FAM111A-related Kenny-Caffey syndrome reported in the literature
From: Homozygous synonymous FAM111A variant underlies an autosomal recessive form of Kenny-Caffey syndrome
| Ā | Family in this study | FAM111A-related Kenny-Caffey syndrome | |
|---|---|---|---|
Patient 1 | Patient 2 | 46 patients from 38 families reported in the literature | |
General information | |||
āFAM111A variant (NM_001312909.2) | c.81āGā>āA (homozygous), r.[81āgā>āa, -37_81del, 50_81del] | heterozygous missense and in-frame deletion variants (see Fig. S1) | |
āPrenatal findings | NA | NA | intrauterine growth retardation (7/24) |
Craniofacial abnormalities | |||
āAbnormality of the face | triangular face, prominent forehead, high anterior hairline, underdeveloped supraorbital ridges | triangular face, prominent forehead, high anterior hairline | triangular face (12/18), prominent forehead (26/29), narrow palpebral fissures (13/20), midface retrusion (8/19) |
āAbnormal ear morphology | low-set, posteriorly rotated ears, small earlobes, prominent antihelix | low-set, posteriorly rotated ears, prominent antihelix | low-set ears (9/20) |
āAbnormal eye morphology | deeply set eyes, narrow palpebral fissures, bilateral microphthalmos, blue sclerae, hypotelorism, abnormal optic disc morphology, hypopigmentation of the fundus, dilatation of large choroidal vessels | deeply set eyes, bilateral microphthalmos, blue sclerae, hypotelorism, abnormal optic disc morphology, hypopigmentation of the fundus, dilatation of large choroidal vessels | deeply set eyes (7/8), microphthalmia (4/22), papilledema/pseudopapilledema (4/21) |
āAbnormal nasal morphology | prominent nasal bridge, long and narrow nose, low hanging columella, underdeveloped nasal alae | narrow nose | short nose and narrow nasal ridge (5/15) |
āAbnormal oral morphology | short philtrum, thick lower lip vermilion | thick lower lip vermilion, downturned corners of mouth | thin upper lip vermilion (5/8) |
āAbnormality of the dentition | microdontia of primary teeth | ā | enamel hypoplasia, microdontia, hypodontia/oligodontia and/or abnormality of dental eruption (17/22), carious teeth (9/17), premature loss of secondary dentition (4/14) |
Abnormal eye and ear physiology | |||
āAbnormality of refraction | high hypermetropia, astigmatism, fully accommodative esotropia, strabismus | high hypermetropia, astigmatism, fully accommodative esotropia | hypermetropia or myopia and/or astigmatism (29/35) |
āHearing abnormality | ā | ā | hearing impairment (4/9) |
Abnormal skeletal morphology | |||
āAbnormality of body height | short stature | short stature | short stature/postnatal growth retardation (40/43) |
āAbnormality of skull size | relative macrocephaly | ā | microcephaly (1 patient), relative macrocephaly (7 patients) |
āAbnormal skull morphology | dolichocephaly, thickened calvaria | dolichocephaly | craniosynostosis (4/21), wide anterior fontanel/delayed closure of the anterior fontanel (26/32), decreased skull ossification (3/11), micrognathia or microretrognathia (15/21), mandibular prognathia (1 patient) |
āAbnormal axial skeleton morphology | pectus carinatum, thoracic scoliosis | ā | scoliosis (3 patients), thin ribs (1/21) |
āSubperiosteal bone formation | yes | yes | ā |
āAbnormal long bone morphology | thickened cortex of long bones, stenosis of the medullary cavity of the long bones, slender long bones | thickened cortex of long bones, stenosis of the medullary cavity of the long bones | cortical thickening of long bones (31/36), stenosis of medullary cavity of long bones (32/36), slender long bones (6/24) |
āAbnormal limb bone morphology | ā | ā | acromicria (3/22) |
āAbnormality of skeletal maturation | delayed skeletal maturation | delayed skeletal maturation | delayed skeletal maturation (4 patients) |
Miscellaneous | |||
āNeurodevelopmental abnormalities | ā | ā | intellectual disability (5/19) |
āAbnormality of the integument | thin skin, sparse scalp hair, sparse eyebrows, nail dysplasia | hypermelanotic macule, sparse scalp hair, sparse eyebrows, nail dysplasia | sparse scalp hair (6 patients), nail dysplasia (2 patients) |
āAbnormality of the voice | high-pitched voice, hypernasal speech | high-pitched voice, nasal speech | high-pitched voice (2 patients) |
āAbnormality of the respiratory system | pulmonary hypoplasia | ā | respiratory distress (1 patient) |
āAbnormality of the genital system | ā | micropenis, cryptorchidism | micropenis (4 patients), decreased testicular size (5 patients) |
āAbnormality of blood and blood-forming tissues | anemia, thrombocytosis | anemia, thrombocytosis | anemia (1 patient) |
āAbnormality of the endocrine system and of circulating metabolite concentration | reduced circulating growth hormone concentration, decreased response to growth hormone stimulation test | ā | primary hypoparathyroidism with hypocalcemia and/or hyperphosphatemia (40/46), hypomagnesemia (14/21), hypokalemia (4/6), reduced circulating growth hormone concentration (5 patients) |
āOther abnormalities | recurrent infections, prominent superficial veins, spina bifida occulta at L5 | spina bifida occulta at L5 | recurrent infections (5 patients), chronic kidney disease (6/9), other renal insufficiency (3 patients) |
