Genetic Syndromes

Gene/chromosome: Trisomy 21; Inheritance: Usually meiotic nondisjunction, sporadic; Triad: Hypotonia, epicanthic folds, single palmar crease; Associated: AV septal defect, ALL/AML, early Alzheimer disease; Investigation: Karyotype, FISH

Gene/chromosome: Trisomy 18; Inheritance: Usually meiotic nondisjunction, sporadic; Triad: Clenched overlapping fingers, rocker-bottom feet, prominent occiput; Associated: VSD, PDA; Investigation: Karyotype

Gene/chromosome: Trisomy 13; Inheritance: Usually meiotic nondisjunction, sporadic; Triad: Holoprosencephaly, cleft lip/palate, polydactyly; Associated: VSD, PDA; Investigation: Karyotype

Gene/chromosome: 45,X; Inheritance: Usually sporadic chromosomal nondisjunction; Triad: Short stature, webbed neck, streak ovaries; Associated: Coarctation of aorta, bicuspid aortic valve; Investigation: Karyotype, absent Barr body

Gene/chromosome: 47,XXY; Inheritance: Usually sporadic nondisjunction; Triad: Tall stature, small firm testes, gynecomastia; Associated: Germ cell tumors, mediastinal tumors; Investigation: Karyotype, one Barr body

Gene/chromosome: 47,XXX; Inheritance: Usually sporadic nondisjunction; Triad: Tall stature, learning difficulties, premature ovarian insufficiency; Associated: Usually no characteristic CHD or malignancy; Investigation: Karyotype

Gene/chromosome: 47,XYY; Inheritance: Usually sporadic nondisjunction; Triad: Tall stature, speech/learning difficulties, behavioral difficulties; Associated: No characteristic CHD or malignancy; Investigation: Karyotype

Gene/chromosome: FMR1, Xq27.3; Inheritance: X-linked dominant with variable expression; Triad: Long face, large ears, macroorchidism; Associated: No characteristic CHD or malignancy; Investigation: CGG repeat analysis, methylation testing

Gene/chromosome: 15q11-q13; Inheritance: Loss of paternal expression; Triad: Neonatal hypotonia, hyperphagia, hypogonadism; Associated: Obesity-related complications; Investigation: Methylation analysis, microarray

Gene/chromosome: 15q11-q13, UBE3A; Inheritance: Loss of maternal expression; Triad: Severe intellectual disability, ataxia, inappropriate laughter; Associated: Seizures; Investigation: Methylation analysis, UBE3A testing

Gene/chromosome: 7q11.23 deletion, ELN; Inheritance: Usually de novo autosomal dominant microdeletion; Triad: Elfin facies, hypercalcemia, sociable personality; Associated: Supravalvular aortic stenosis; Investigation: FISH, microarray

Gene/chromosome: 22q11.2 deletion, TBX1 region; Inheritance: Usually de novo autosomal dominant microdeletion; Triad: Thymic hypoplasia, hypocalcemia, conotruncal defects; Associated: Tetralogy of Fallot, truncus arteriosus; Investigation: FISH, microarray, low T cells

Gene/chromosome: 11p13 deletion, WT1/PAX6; Inheritance: Usually de novo deletion; Triad: Wilms tumor, aniridia, genitourinary anomalies; Associated: Wilms tumor; Investigation: Karyotype, FISH, microarray

Gene/chromosome: 11p15 imprinting region, IGF2/CDKN1C; Inheritance: Imprinting defect, usually sporadic; Triad: Macroglossia, omphalocele, macrosomia; Associated: Wilms tumor, hepatoblastoma; Investigation: Methylation analysis, molecular testing

Gene/chromosome: 11p15 imprinting or maternal UPD7; Inheritance: Imprinting defect or uniparental disomy; Triad: Growth restriction, triangular face, body asymmetry; Associated: Hypoglycemia, feeding difficulties; Investigation: Methylation analysis, UPD testing

Gene/chromosome: CHD7, chromosome 8; Inheritance: Autosomal dominant, usually de novo; Triad: Coloboma, choanal atresia, ear anomalies; Associated: Congenital heart defects; Investigation: CHD7 sequencing

Gene/chromosome: Heterogeneous, no single gene; Inheritance: Usually sporadic, multifactorial; Triad: Vertebral, anal, cardiac, tracheoesophageal, renal, limb anomalies; Associated: VSD, other congenital heart defects; Investigation: Clinical diagnosis, targeted imaging

Gene/chromosome: Heterogeneous, sometimes SOX9; Inheritance: Variable; Triad: Micrognathia, glossoptosis, cleft palate; Associated: Airway obstruction; Investigation: Clinical examination, airway assessment

Gene/chromosome: TCOF1, chromosome 5; Inheritance: Autosomal dominant; Triad: Mandibular hypoplasia, downslanting palpebral fissures, malformed ears; Associated: Conductive hearing loss; Investigation: TCOF1 molecular testing, audiology

Gene/chromosome: PTPN11 and RAS-MAPK pathway genes; Inheritance: Autosomal dominant; Triad: Short stature, webbed neck, hypertelorism; Associated: Pulmonary stenosis, hypertrophic cardiomyopathy; Investigation: Molecular genetic panel

Gene/chromosome: FGFR2, chromosome 10; Inheritance: Autosomal dominant; Triad: Craniosynostosis, midface hypoplasia, syndactyly; Associated: Airway obstruction, congenital heart defects occasionally; Investigation: FGFR2 sequencing, CT skull

Gene/chromosome: FGFR2, chromosome 10; Inheritance: Autosomal dominant; Triad: Craniosynostosis, proptosis, midface hypoplasia; Associated: No characteristic CHD; Investigation: FGFR2 sequencing, CT skull

Gene/chromosome: Heterogeneous, often sporadic; Inheritance: Usually sporadic; Triad: Hemifacial microsomia, epibulbar dermoid, vertebral anomalies; Associated: VSD, other cardiac defects occasionally; Investigation: Clinical examination, imaging

Gene/chromosome: COL4A5 X-linked or COL4A3/COL4A4; Inheritance: X-linked or autosomal recessive/dominant; Triad: Hematuria, sensorineural deafness, ocular abnormalities; Associated: Progressive CKD; Investigation: Urinalysis, renal biopsy, genetic testing

Gene/chromosome: DNAH5/DNAI1 and other ciliary genes; Inheritance: Usually autosomal recessive; Triad: Situs inversus, bronchiectasis, chronic sinusitis; Associated: Infertility; Investigation: Nasal nitric oxide, ciliary studies, genetic testing

Gene/chromosome: CFTR, chromosome 7; Inheritance: Autosomal recessive; Triad: Recurrent pulmonary infections, pancreatic insufficiency, elevated sweat chloride; Associated: Meconium ileus, bronchiectasis; Investigation: Sweat chloride test, CFTR testing