67 Noonan Syndrome
NS1, Male Turner-like syndrome
Short stature, broad forehead, ptosis, low-set ears, pterygium colli, low posterior hairline, shield chest, heart defects
Frequency: 1 in 5,000 births. Over 400 cases reported.
Genetics
Autosomal dominant (OMIM 163950), with variable expression; caused by mutation in the PTPN11 gene at 12q22-qter; allelic to LEOPARD syndrome, Noo- nan-like multiple giant cell lesion syndrome, and cardio-facio-cutaneous syndrome.
Clinical Features
• Short stature
• Broad and tall forehead, triangular face
• Hypertelorism, ptosis, down-slanting palpebral fissures, epicanthal folds
• Flat nasal bridge
• Deeply grooved philtrum, high-arched palate (45%), malocclusion
• Micrognathia (25%)
• Low-set, posteriorly rotated ears (90%)
• Posterior cervical hygroma, short webbed neck, pterygium colli, low posterior hairline (55%), coarse hair
• Shield chest
• Kyphoscoliosis
• Congenital heart defect (pulmonary valve steno- sis, septal defects, tetralogy of Fallot) (65%)
• Ocular anomalies (strabismus, nystagmus, ambly- opia, anterior segment anomalies)
• Kidney anomalies (hydronephrosis, duplication of ureters, renal hypoplasia/aplasia), hepatospleno- megaly, skin lesions (café-au-lait spots, pigmented nevi, lentigines, hyperkeratosis), hematological abnormalities (bleeding disorders, pancytopenia), malignant hyperthermia, behavioral problems, hypoplasia/aplasia of the lymphatic channels
Differential Diagnosis
• 45,X Turner syndrome
• Cardio-facio-cutaneous syndrome
• Watson syndrome
• Neurofibromatosis
• LEOPARD syndrome
Radiographic Features Skull
• Orbital hypertelorism
• Parietal foramina
• Bitemporal bulging
• Inclination of anterior fossa
• Micrognathia
• Dental malocclusion Spine
• Kyphoscoliosis
• Klippel-Feil anomaly
• Vertebral fusion Generalized Bone Defects
• Retarded bone age
Noonan Syndrome 780
Fig. 67.1. Patient 1, age 5 years. Broad and tall forehead, hyper- telorism, ptosis, down-slanting palpebral fissures, low-set ears, short and webbed neck, and mild pectus excavatum
Chest
• Pectus carinatum in upper and excavatum in lower part (90%), broad thorax
• Scapula alata, rounded shoulders
• Cervical ribs Limbs
• Cubitus valgus (50%)
• Genu valgum
• Pes planum
• Syndactyly, camptodactyly, brachydactyly
• Clinodactyly of 5th fingers
• Radial head dislocation Joints
• Joint contractures (4%), hyperextensible joints (30%)
Bibliography
Allanson JE. Noonan syndrome. J Med Genet 1987; 24: 9–13 Canepa G, Maroteaux P, Pietrogrande V. Sindromi dismorfiche
e malattie costituzionali dello scheletro. Piccin, Padova, 1996
Collins E, Turner G. The Noonan syndrome – a review of the clinical and genetic features of 27 cases. J Pediatr 1973; 83:
941–50
Duncan WJ, Fowler RS, Farkas LG, Ross RB, Wright AW, Bloom KR, Huot DJ, Sondheimer HM, Rowe RD. A comprehensive scoring system for evaluating Noonan syndrome.Am J Med Genet 1981; 10: 37–50
Jamieson CR, van der Burgt I, Brady AF, van Reen M, Elsawi MM, Hol F, Jeffery S, Patton MA, Miarman E. Mapping a gene for Noonan syndrome to the long arm of chromo- some 12. Nat Genet 1994; 8: 357–60
Marino B, Digilio MC, Toscano A, Giannotti A, Dallapiccola B.
Congenital heart disease in children with Noonan syn- drome: an expanded cardiac spectrum with high preva- lence of atrioventricular canal. J Pediatr 1999; 135: 703–6 Mendez HMM, Opitz JM. Noonan syndrome: a review. Am J
Med Genet 1985; 21: 493–506
Noonan JA. Noonan syndrome. An update and review for the primary pediatrician. Clin Pediatr 1994; 33: 548–55 Ranke MB, Heidemann P, Knupfer C, Enders H, Schmaltz AA,
Bierich JR. Noonan syndrome: growth and clinical mani- festations in 144 cases. Eur J Pediatr 1988; 148: 220–7 Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG,
Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 2001; 29: 465–8
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Fig. 67.2 a, b. Patient 2, age 14 years. a Triangular face, broad forehead, hypertelorism, ptosis, down-slanting palpebral fissures, low-set ears, and b pterygium colli
a b
Noonan Syndrome 782
Fig. 67.3. Patient 3, age 3 years.
Segmentation anomalies (fusion) of the cervical vertebrae. (Reprint- ed, with permission, from Canepa et al. 1996)
