Chromosomal disorders
Trisomy 21 (Down Syndrome)
General Features:
Muscular hypotonia
Transient myelodysplasia of the newborn
Head:
Brachycephaly
Oblique palpebral fissures
Epicanthic folds
Brushfield's spots (ring of iris speckles)
Ears set low, folded, or stenotic meatus
Mouth:
Protruding tongue (small, narrow palate)
High arched palate
Neck:
Loose skin on the nape of the neck
Hands:
Single palmar crease
Short little finger
Feet:
Gap between hallux and second toes
Cardiovascular:
Atrioventricular septal defect (AVSD)
Gastrointestinal:
Duodenal atresia
Hirschprung disease in 2% (12% of HD patients have T21)
Renal:
Mild antenatal hydronephrosis
Trisomy 18 (Edwards Syndrome)
General Features:
Neonatal hypotonia followed by hypertonia
Delayed psychomotor development and intellectual disability
Skull:
Microcephaly
Bitemporal narrowing
Prominent occiput
Face:
Triangular and asymmetric face with facial paralysis
Eyes:
Microphthalmia
Hypertelorism
Epicanthus
Short palpebral fissures
Coloboma of iris
Cataract
Upward or downward slanting palpebral fissures
Nose:
Prominent nasal bridge
Hypoplastic nasal root
Upturned nares
Choanal atresia
Oral Cavity:
Micro-retrognathia
Microstomia
Narrow arched palate
Cleft lip and palate
Ears:
Microtia
Preauricular appendages
Low-set or retroverted ears
Chest and Thorax:
Short neck
Short sternum
Broad chest, with or without widely spaced small nipples
Incomplete ossification of the clavicle
Pectus excavatum
Cardiac defects
Pulmonary hypoplasia
Tracheobronchomalacia
Laryngomalacia
Gastrointestinal:
Omphalocele
Oesophageal atresia with tracheoesophageal fistula
Pyloric stenosis
Ileal atresia
Malrotation
Diastasis recti
Genitourinary:
Cryptorchidism
Hypospadias
Micropenis
Clitoral hypertrophy
Ovarian dysgenesis
Bifid uterus
Horseshoe kidney
Renal agenesis
Skeletal:
Hemivertebrae or fused vertebrae
Scoliosis
Hip dislocation
Arthrogryposis
Syndactyly
Single palmar crease
Radial or thumb hypoplasia
Hypoplastic nails
Rocker-bottom feet with prominent calcaneus
Talipes equinovarus
Neurological:
Meningoencephalocele
Anencephaly
Hydrocephalus
Holoprosencephaly
Arnold-Chiari malformation
Trisomy 13 (Patau Syndrome)
Craniofacial:
Cleft lip and palate
Microphthalmia or anophthalmia
Capillary hemangiomata
Hands:
Simian creases
Polydactyly
Trigger thumbs
Cerebral:
Severe cerebral defects
Renal:
Horseshoe kidneys
Turner Syndrome
Craniofacial:
Eyes: epicanthic folds, oblique palpebral fissures
Ears: low-set
Mouth: micrognathia, high arched palate
Neck:
Short and webbed
Low hairline
Thorax:
Broad chest
Pectus excavatum
Hands:
Short 4th/5th metacarpals
Skin:
Lymphoedema
Risk of keloid formation post-surgery
Cardiovascular:
Coarctation of the aorta
Bicuspid aortic valve
Aortic stenosis
Aortic aneurysms
Mitral valve prolapse
Ectopia cordis
Hypoplastic left heart
Pulmonary stenosis
Vascular:
Vascular malformations
Conduction defects (including prolonged QT interval)
Renal:
Duplex kidneys
Absent kidney
Malrotation
Horseshoe kidneys
Gonadal:
Gonadal dysgenesis or failure
Fibrotic ovarian streaks at birth
Recommended removal of bilateral streak gonads before school age in 45,XO/46,XY mosaics
Approximately 30% of girls with Turner syndrome have some spontaneous pubertal development
Klinefelter Syndrome
Genetic Basis:
Extra X chromosome (47,XXY, 48,XXXY polysomy, or mosaic 47,XXY/46,XY)
Barr body formation in somatic cells
Clinical Features:
Infertility or subfertility
Small, firm testes, may be undescended
Decreased facial and pubic hair
Loss of libido
Tall and slender with long legs, narrow shoulders, and wide hips
Gynaecomastia or history of gynaecomastia during puberty
Decreased libido
Learning disability
22q11 Microdeletion Syndrome (DiGeorge Syndrome)
Part of 22q11 Deletion Syndromes:
Includes Velocardiofacial syndrome, Cayler cardiofacial syndrome, Sedlackova syndrome, conotruncal anomaly face syndrome
Clinical Features:
Pharyngeal arch anomalies
Cardiac anomalies (especially conotruncal cardiac anomalies)
Recurrent infections
Abnormal facies
Thymic hypoplasia or aplasia
Cleft palate
Developmental delay
Hypoparathyroidism leading to hypocalcaemia
Diagnosis:
FISH, Array CGH
Investigations:
Echocardiography
Parathyroid hormone (PTH) and calcium levels
Serum immunoglobulins
Thyroid-stimulating hormone (TSH)
Chest X-ray (CXR)
Velocardiofacial (VCF) or Shprintzen Syndrome:
Autosomal dominant
Clinical Features: cleft palate, cardiac anomalies, distinct facial features, learning disabilities
Management: Candidates for cleft palate repair, CT angiography to verify the location of the internal carotid arteries
Fragile X Syndrome
Genetic Basis:
Expansion of the CGG triplet repeat within the FMR1 gene on the X chromosome (X-linked dominant)
Clinical Features:
Long and narrow face
Large ears
Flexible fingers
Macroorchidism (large testes)
Severe intellectual disability
Wolf-Hirschhorn Syndrome
Genetic Basis:
4p16 deletion
Autosomal recessive
Clinical Features:
Microcephaly
Micrognathia
Ocular hypertelorism
Dysplastic ears with periauricular tags
Growth restriction
Intellectual disability
Muscle hypotonia
Seizures
Congenital heart defects
Renal agenesis/dysplasia
Bladder extrophy
Obstuctive uropathy
Less common: hypospadias, colobomata of the iris, renal anomalies, deafness
Fryn Syndrome
Clinical Features:
Diaphragmatic defects (hernia, eventration, hypoplasia, or agenesis)
Coarse facies with wide-set eyes
Short distal phalanges of fingers and toes
Pulmonary hypoplasia
Polyhydramnios
Cloudy corneas and/or microphthalmia
Orofacial clefting
Renal dysplasia or renal cortical cysts
Prognosis:
Survival beyond the neonatal period is rare
References
Akhtar F, Bokhari SRA. Down Syndrome. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526016/
Balasundaram P, Avulakunta ID. Edwards Syndrome. [Updated 2023 Mar 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK570597/
Williams GM, Brady R. Patau Syndrome. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538347/
Shankar Kikkeri N, Nagalli S. Turner Syndrome. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554621/
Los E, Leslie SW, Ford GA. Klinefelter Syndrome. [Updated 2023 Nov 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482314/
Lackey AE, Muzio MR. DiGeorge Syndrome. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549798/
Stone WL, Basit H, Shah M, et al. Fragile X Syndrome. [Updated 2023 Oct 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459243/
Popescu DE, Marian D, Zeleniuc M, Samoila C, Belengeanu V. Features of the Wolf-Hirschhorn Syndrome (WHS) from Infant to Young Teenager. Balkan J Med Genet. 2023 Jul 31;26(1):75-82. doi: 10.2478/bjmg-2023-0006. PMID: 37576793; PMCID: PMC10413881.
Slavotinek A. Fryns Syndrome. 2007 Apr 18 [updated 2020 Sep 17]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301632.