Table 2. Overview of testing done for 41 affected and 19 unaffected individuals.
| Family | Sample | Gender | Genetic testing | Variants identified | MLPA | Clinical features | BMKS/isolated choanal atresia |
|---|---|---|---|---|---|---|---|
| Family 1 | III.2 | F | TCOF1, CHD7, SNP array, WGS | hg19 chr18:g.77748581_77748614del (1Δ) (M), c.258-2A>G, (p.?) (P) | Y | Normal pregnancy, facial asymmetry, short palpebral fissures, defect of lower eyelids, aplasia of puncta lacrimalis L, hypoplasia infra-orbital rim R, upslanting palpebral fissures, longer eyelashes laterally than medially, choroid coloboma L, microstrabismus, amblyopia bilateral choanal atresia, preauricular tag R, maxillary hypoplasia R, micrognathia R and normal psychomotor development | BMKS |
| II.1 | M | WGS | c.258-2A>G, (p.?) | Y | Scleral show | ||
| II.2 | F | WGS | hg19 chr18:g.77748581_77748614del (1Δ) | Y | |||
| Uncle | M | TXNL4A | Y | ||||
| Husband | M | TXNL4A | Y | ||||
| Family 2 | III.1 | M | Affymetrix 750 K microarray, TXNL4A | hg19 chr18:g.77748581_77748614del (1Δ) (P), c.258-2A>G, (p.?) (M) | Y | Polyhydramnios, bilateral defect of lower eyelids, hypermetropia, prominent nasal bridge, cleft lip and palate L, bilateral choanal atresia, preauricular tag R, micrognathia, normal psychomotor development, dimple on the cheek, asymptomatic ASD and VSD | BMKS |
| II.2 | F | TXNL4A | c.258-2A>G, (p.?) | N | |||
| II.1 | M | TXNL4A | hg19 chr18:g.77748581_77748614del (1Δ) (het) | N | |||
| Family 3 | III.1 | M | Affymetrix 750 K microarray -> isodisomy of chr18 TXNL4A | hg19 chr18:g.77748581_77748614del (1Δ) (hom) | Y | IVF ICSI, failure to progress and bilateral choanal atresia | Choanal atresia |
| II.2 | F | TXNL4A | hg19 chr18:g.77748581_77748614del (1Δ) (het) | N | |||
| II.1 | M | TXNL4A | hg19 chr18:g.77748581_77748614del (1Δ) (het) | N | |||
| Family 4 | V.4 | M | TXNL4A, TBX22 | hg19 chr18: g.77748604_77748637del (2Δ) (hom) | Y | Polyhydramnios, downslanting palpebral fissures, prominent nasal bridge, bilateral choanal atresia, maxillary hypoplasia, prognathism, high arched narrow palate, absence of the upper and lower deciduous premolars, hypodontia of four permanent premolars and normal psychomotor development | Choanal atresia |
| V.6 | F | Karyo, TXNL4A, TBX22 | c.-245_-212del34, (p.?) (2Δ) (hom) | Y | Polyhydramnios, prominent nasal bridge, bilateral choanal atresia, maxillary hypoplasia, cowlick, downslanting palpebral fissures, prognathism, dental malocclusion, narrow palate and unilateral absence of the permanent upper lateral incisor | Choanal atresia | |
| III.1 | F | TXNL4A | N | ||||
| III.2 | F | TXNL4A | hg19 chr18: g.77748604_77748637del (2Δ) (het) | N | |||
| IV.1 | F | TXNL4A | N | ||||
| IV.2 | M | TXNL4A | hg19 chr18: g.77748604_77748637del (2Δ) (het) | N | Prognathism | ||
| IV.3 | F | TXNL4A | N | ||||
| IV.4 | M | TXNL4A | hg19 chr18: g.77748604_77748637del (2Δ) (het) | N | |||
| IV.5 | M | TXNL4A | hg19 chr18: g.77748604_77748637del (2Δ) (het) | N | Prognathism | ||
| IV.6 | M | TXNL4A | hg19 chr18: g.77748604_77748637del (2Δ) (het) | N | |||
| IV.7 | F | TXNL4A | hg19 chr18: g.77748604_77748637del (2Δ) (het) | N | |||
| V.1 | F | TXNL4A | N | ||||
| V.2 | M | TXNL4A | N | ||||
| V.3 | M | TXNL4A | N | ||||
| V.5 | M | TXNL4A | hg19 chr18: g.77748604_77748637del (2Δ) (het) | N | |||
| V.7 | M | TXNL4A | hg19 chr18: g.77748604_77748637del (2Δ) (het) | N | |||
| Family 5 | II.1 | M | WGS, TXNL4A | Y | Ptosis, shallow orbits, prominent beaked nose and micrognathia | BMKS | |
| I.2 (mother) | F | WGS, TXNL4A | Y | ||||
| 6 | M | WGS, TXNL4A, TCOF1, POLR1D, POLR1C, POLR1A, array | Y | Polyhydramnios, premature, respiratory distress, macroglossia, micrognathia, retrognathia, cleft palate, bilateral microtia, preauricular fistula, short downslanting palpebral fissures, shallow orbits and hearing loss | BMKS | ||
| 7 | M | TXNL4A, array, TCOF1, SALL1, POLR1C, POLR1D | Y | Small for gestational age, conductive hearing loss, bilateral ear tags, downslanting palpebral fissures, hypertelorism, micrognathia, perianal tag and patent foramen ovale | BMKS | ||
| 8 | F | TXNL4A, CHD7 | Y | Bilateral choanal atresia | Choanal atresia | ||
| 9 | F | TXNL4A | Y | Bilateral Tessier 7 cleft, dental crowding, bilateral ear tags, hearing loss based on absent cochlear nerves, coloboma of the left papill, retina and pupil, amblyopia, esophageal atresia with tracheoesophageal fistula, hemivertebrae, hypoplastic thumbs L>R, bilateral hemifacial macrosomia, hypotonia, OSA and mild PMR | BMKS | ||
| 10 | M | Karyo, TXNL4A | Y | Micrognathia, retrognathia, narrow maxilla, bilateral ear tags, hearing loss, epibulbar dermoid (R), dental crowding and OSA | BMKS | ||
| 11 | F | All TCS genes, WES, BOR genes | Y | Asymmetry of the face, hearing loss, normal stature, dysplastic ears, amblyopia and aberrant facial nerve | BMKS | ||
| 12 | F | TCOF1, POLR1C, POLR1D, WES, TXNL4A | deletion of POLR1D | Y | Asymmetry of the face, hypertelorism, short palpebral fissures, prominent nasal bridge, cleft lip and palate, microtia, maxillary hypoplasia, micrognathia, hearing loss, normal psychomotor development and short stature | BMKS | |
| 13 | M | all TCS genes, TXNL4A | Y | Unilateral cleft lip and palate, maxillary hypoplasia, micrognathia and normal psychomotor development | BMKS | ||
| 14 | M | TCOF1, array, BOR syndrome genes, TXNL4A | Y | Renal cysts and microtia (unilateral) | BMKS | ||
| 15 | F | TCOF1, SNP array, POLR1C, POLR1D, TXNL4A | Y | Bilateral preauricular tags, bilateral Tessier 7 cleft, microtia R and anal atresia | BMKS | ||
| 16 | M | TCOF1, TXNL4A | Y | Maxillary hypoplasia, micrognathia, microtia R and hypoplasia zygomata (mild) | BMKS | ||
| 17 | M | TCOF1, TXNL4A | Y | Maxillary hypoplasia, micrognathia and unilateral hearing loss | BMKS | ||
| 18 | TXNL4A, TBX22 | Y | Hypertelorism, hypoplastic uvula, right sided choanal atresia, Mum Carbimazole treatment, blue eyes and ear pit (cochlear implant) | Choanal atresia | |||
| 19 | TXNL4A, TBX22 | Y | Choanal atresia R | Choanal atresia | |||
| 20 | TXNL4A, TBX22 | Y | Choanal atresia B | Choanal atresia | |||
| 21 | TXNL4A, TBX22 | Y | Choanal atresia R | Choanal atresia | |||
| 22 | TXNL4A, TBX22 | Y | Bifid uvula, choanal atresia R, ASD | Choanal atresia | |||
| 23 | TXNL4A, TBX22 | Y | Choanal atresia R | Choanal atresia | |||
| 24 | TXNL4A, TBX22 | N | Choanal atresia R | Choanal atresia | |||
| 25 | TXNL4A, TBX22 | N | Choanal atresia | ||||
| 26 | CHD7, TXNL4A, TBX22 | R157X in CHD7 | N | CHARGE | Choanal atresia | ||
| 27 | TXNL4A, TBX22 | N | Choanal atresia | ||||
| 28 | TXNL4A, TBX22 | N | Choanal atresia | ||||
| 29 | TXNL4A, TBX22 | N | Choanal atresia | ||||
| 30 | TXNL4A, TBX22 | N | Choanal atresia | ||||
| 31 | TXNL4A, TBX22 | N | Choanal atresia L, ID and syngnathia | Choanal atresia | |||
| 32 | TXNL4A | N | BMKS | ||||
| 33 | F | TXNL4A | N | BMKS | |||
| 34 | M | TXNL4A | N | BMKS | |||
| 35 | M | TXNL4A | N | BMKS | |||
| 36 | M | TXNL4A | N | BMKS |
Abbreviations: ASD, arial septal defect; B, bilateral; f, female; Hom, homozygous; ICSI, intracytoplasmic sperm injection; ID, intellectual disability; IVF, in vitro fertilization; karyo, karyogram; L, left; m, male; M, maternal; N, no; OSA, obstructive sleep apnea; P, paternal; PMR, psychomotor retardation; R, right; VSD, ventricular septal defect; WES, whole-exome sequencing; WGS, whole-genome sequencing; Y, yes.