Physical Symptoms of Common Genetic Syndromes: Overview

Genetic syndromes have recognizable phenotypic patterns. This overview highlights cardinal features for clinical recognition.

Down Syndrome (Trisomy 21)

• Flat facial profile, upslanting palpebral fissures, epicanthal folds, Brushfield spots.
• Small ears, protruding tongue, single palmar crease, sandal gap.
• Hypotonia, intellectual disability, congenital heart defects (AVSD 40%).

Fragile X Syndrome

• Long face, large ears, prominent forehead/jaw, macroorchidism (post-pubertal).
• Intellectual disability, autism features, hyperactivity, mitral valve prolapse.

Marfan Syndrome (FBN1)

• Tall, disproportionate long limbs (arm span > height), arachnodactyly.
• Lens dislocation (ectopia lentis), aortic root dilation/dissection, pectus deformity, scoliosis.

Neurofibromatosis Type 1 (NF1)

• ≥6 café-au-lait macules (>5 mm prepubertal, >15 mm post), axillary/inguinal freckling.
• Neurofibromas (cutaneous, plexiform), Lisch nodules (iris hamartomas).
• Optic glioma, skeletal dysplasia, learning disabilities.

Prader-Willi Syndrome (15q11-q13 del/mat UPD)

• Neonatal hypotonia, poor feeding → hyperphagia/obesity in childhood.
• Short stature, small hands/feet, hypogonadism, intellectual disability, behavioral issues.

Rett Syndrome (MECP2)

• Normal early development → regression (6–18 mo): loss of speech, purposeful hand use; stereotypic hand wringing.
• Seizures, scoliosis, breathing irregularities, growth failure.

Turner Syndrome (45,X)

• Short stature, webbed neck, low hairline, broad chest (shield), lymphedema (infants).
• Gonadal dysgenesis (streak ovaries), cardiac (bicuspid aortic valve, coarctation), renal, autoimmune.

Williams Syndrome (7q11.23 del)

• “Elfin” facies: periorbital fullness, stellate iris, wide mouth, full lips.
• Supravalvular aortic stenosis, hypercalcemia, ID, hypersociability, anxiety.

Recognition enables early syndrome-specific surveillance (cardiac, endocrine, developmental) and genetic counseling.