This issue of eMedRef provides information to clinicians on the pathophysiology, diagnosis, and therapeutics of common syndromes and sequences fund with dysmorphic features

Cole, Sarah

Taylor, Matthew

English

University of Missouri: MOspace

Dysmorphic Features Syndromes and Sequences        Page 1 of 5   7.7.10 Dysmorphic Features:  Common Syndromes and Sequences Background 1. Dysmorphic features:  o Abnormal body variations that can be measured or characterized (congenital anomalies or "birth defects")   Singular anomalies often diagnostically insignificant  Multiples anomalies can aid in diagnosis of a larger syndromes 2. Epidemiology of dysmorphology  o Incidence of major malformations is approximately 2-3% of live births o Congenital malformations account for approximately 20% of infant deaths  3. This summary is limited to common congenital sequences and syndromes  Pathophysiology 1. Etiology is diverse but may include genetic, infectious, chemical or metabolic causes  o Physical causes may include decreased amniotic fluid, compression, torsion 2. Different organ systems are susceptible to teratogenesis during different stages of development  o Most major malformations occur in the embryonic period (3 to 8 wks) o Functional defects and minor malformations may occur throughout the fetal period (9-38 wks)   CNS, sensory organs, teeth, and external genitalia remain susceptible  Common Congenital Sequences and Syndrome 1. Autosomal syndromes  o General patterns   Frequency of chromosomal disorders increases with maternal age  Frequency of recurrence depends on whether the cause is a chromosomal translocation (higher recurrence risk, independent of maternal age) o Trisomy 21   M/c pattern of malformation (approximately 1 in 660 infants)  Most cases are full trisomy 21; a minority (approximately 5%) are either mosaic or translocation  Clinical findings   Mental deficiency  Hypotonia, hyperflexibility of joints, flat facial profile, protruding tongue, loose nuchal skin  White specks on iris (Brushfield spots)  Single transverse palmar crease  Pelvic dysplasia  Wide gap between first and second toes ("sandal gap")  Associated with cardiac defects (approx 40% of cases), immune dysfunction, lymphoma, atlantoaxial dislocation  Dysmorphic Features Syndromes and Sequences        Page 2 of 5   7.7.10  Resources for patients and families available at http://www.ndss.org/ o Trisomy 18   Approximately 3 in 1000 newborns   Ratio 3:1 female:male  Almost all cases are full trisomy without translocation; therefore recurrence risk is low (less than 1%)  Clinical findings   Severe mental deficiency  Feeble activity, weak cry, micrognathia  With clenched fist, overlapping of index finger over third, fifth finger over fourth  Hypoplasia of nails  Mild hirsutism of forehead and back  Associated with cardiac defects, horseshoe kidney, cleft lip / palate, and many other defects; median survival time is 14.5 days   Rarely, may survive into childhood (particularly with mosaic or partial trisomy)   Resources for families available at http://www.trisomy18.org/ o Trisomy 13   Approximately 1 in 5000 births  Clinical findings   Severe mental deficiency; holoprosencephaly  Microcephaly, micropthalmia, cleft lip / palate, abnormal auricular helices  Polydactyly, narrow fingernails, single transverse palmar crease  Cryptorchidism, abnormal scrotum in males  Associated with cardiac defects, deafness, polycystic kidney; median survival time is 7 days   Resources for families available at http://www.livingwithtrisomy13.org/ 2. Sex chromosomal syndromes  o XXY syndrome (Klinefelter syndrome)   Approximately 1 in 660 males   Usually diagnosed in adolescence or young adulthood  Diagnosis in childhood is helpful in allowing for testosterone replacement  Clinical findings   Mild mental deficiency (mean IQ between 85 and 90); deficiency particularly in expressive language, processing, and auditory memory  Long limbs, slim stature  Hypogonadism, hypogenitalism  May be associated with severe acne, cryptorchidism, scoliosis, diabetes mellitus (in adulthood), breast cancer, osteoporosis, autoimmune disease   Resources for patients and families available at http://klinefeltersyndrome.org/ Dysmorphic Features Syndromes and Sequences        Page 3 of 5   7.7.10 o 45X syndrome (XO syndrome, Turner syndrome)   Approximately 1 in 2500 newborn females   Most 45X conceptuses die before birth  Clinical findings   Mild mental deficiency (mean IQ 90)  Small stature   Prominent ears, webbed posterior neck, low hairline  Broad chest ("shield chest")  Associated with horseshoe kidney, cardiac defects, ovarian dysgnesis ("streak ovaries")   Resources for patients and families available at http://www.turnersyndrome.org/ 3. Genetic syndromes  o Fragile X syndrome   Approximately 1 in 5000 males; rarer in females   Generally familial (high rate of recurrence)  Clinical findings   Mild to profound mental deficiency  Macrocephaly, long facies, large ears, epicanthal folds  Macrorchidism (post-puberty)  Associated with hyperkinetic behavior, emotional instability, autistic features; abnormalities exist on a continuum depending on the number of repeats   Resources for patients and families available at http://www.fragilex.org/ o Marfan syndrome   Autosomal dominant inheritance  Clinical findings   Normal intelligence, but may show learning disability or attention deficit disorder  Tall stature; long slim limbs; muscular hypotonia  Pectus carinatum  Wrist and thumb sign  Lens subluxation; defect in suspensory ligament  Associated with cardiac defects (esp. dilation of ascending aorta), retinal detachment, diaphragmatic hernia   Resources for patients and families available at http://www.marfan.org/ o Treacher-Collins   Autosomal dominant inheritance  Clinical findings   Malar hypoplasia  Slanting palpebral fissures  Mandibular hypoplasia  Malformation of auricles; external ear canal defect; conductive hearing loss   Dysmorphic Features Syndromes and Sequences        Page 4 of 5   7.7.10  Intelligence is normal   Therefore early recognition of deafness is important  In order to provide hearing aids or surgery for proper development  Plastic surgery in childhood may also offer cosmetic improvement   Resources for patients and families available at http://www.treachercollins.org 4. Teratogenic syndromes  o Fetal alcohol syndrome   Due to exposure of the fetus to alcohol during pregnancy  Clinical findings   Mental retardation (moderate to profound) and brain malformations (e.g. agenesis of corpus callosum)  Smooth philtrum  Maxillary hypoplasia  Microcephaly  Short palpepbral fissures  Nail hypoplasia  Note that there is no "safe" stage during pregnancy to consume alcohol  Resources for patients and families available at http://www.nofas.org/   References 1. Kumar, Praveen & Burton, Barbara K. Congenital malformations: evidence-based evaluation and management. (2008). New York: McGraw Hill Medical. 3-4.  2. Jones, Kenneth Lyons. Smith's Recognizable Patterns of Human Malformation (6th edition). (2006). Philadelphia: Elsevier Saunders. 7-9. 3. Jones, Kenneth Lyons. Smith's Recognizable Patterns of Human Malformation (6th edition). (2006). Philadelphia: Elsevier Saunders. 13-14. 4. Jones, Kenneth Lyons. Smith's Recognizable Patterns of Human Malformation (6th edition). (2006). Philadelphia: Elsevier Saunders. 18-19. 5. Bojesen, Anders, and Claus H Gravholt. "Klinefelter syndrome in clinical practice." Nature Clinical Practice Urology 4.4 (2007): 192. Academic OneFile. Web. 5 Apr. 2010. 6. Jones, Kenneth Lyons. Smith's Recognizable Patterns of Human Malformation (6th edition). (2006). Philadelphia: Elsevier Saunders. 68-69. 7. Jones, Kenneth Lyons. Smith's Recognizable Patterns of Human Malformation (6th edition). (2006). Philadelphia: Elsevier Saunders. 76-77. 8. Jones, Kenneth Lyons. Smith's Recognizable Patterns of Human Malformation (6th edition). (2006). Philadelphia: Elsevier Saunders. 160-161. 9. Jones, Kenneth Lyons. Smith's Recognizable Patterns of Human Malformation (6th edition). (2006). Philadelphia: Elsevier Saunders. 546-547. 10. Jones, Kenneth Lyons. Smith's Recognizable Patterns of Human Malformation (6th edition). (2006). Philadelphia: Elsevier Saunders. 280-281.  Dysmorphic Features Syndromes and Sequences        Page 5 of 5   7.7.10 11. U.S. Preventive Services Task Force. Screening and Behavioral Counseling Interventions in Primary Care to Reduce Alcohol Misuse: Recommendation Statement. April 2004. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/3rduspstf/alcohol/alcomisrs.htm  Authors:  Matthew Taylor, DO, & Sarah Cole, DO, St. Louis University FMRP Editor:  Kara Cadwallader, MD, Rural FMR of Idaho 

Dysmorphic features: common syndromes and sequences

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Dysmorphic features: common syndromes and sequences

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