7 Apert Syndrome
Apert Syndrome 593
Acrocephalosyndactyly Type I, ACS I
Acrobrachycephaly, midface hypoplasia, hypertelorism, proptosis, complete distal fusion of hands and feet Frequency: 1 in 160,000 births.
Genetics
Autosomal dominant (OMIM 101200) with complete penetrance; most cases sporadic; paternal age effect, virtually all mutations paternal in origin; ACS I is due to mutation in the FGFR2 (fibroblast growth factor receptor-2, OMIM 176943) gene, located at 10q25.3–
26; most common mutations affect exon 7 (S252 W and P253R); allelic mutations: Crouzon syndrome, Pfeiffer syndrome (one form), Jackson-Weiss syn- drome, Beare-Stevenson syndrome.
Clinical Features
• Acrobrachycephaly with coronal synostosis
• Flat facies
• Shallow orbits, hypertelorism
• Narrow palate
• Syndactyly (‘baseball glove’ appearance), broad thumb and great toe
• Single nail for digits 2–4
• Progressive fusion of bones of feet during skeletal maturation
• Variable mental retardation
• CNS anomalies common (absent corpus callosum, defects of limbic structures, gyral anomalies, het- erotopic gray matter, ventriculomegaly)
• Cardiovascular defects and genitourinary anom- alies, each in 10% of patients
Differential Diagnosis
• Pfeiffer syndrome
• Crouzon syndrome
• Jackson-Weiss syndrome
Radiographic Features Skull
• Turribrachycephaly with flattened occiput
• Irregular craniosynostosis (coronal sutures most involved)
• Malformed, often asymmetrical, cranial base
• Cloverleaf skull in 4%
• Shallow orbits
• Orbital hypertelorism
• Maxillary hypoplasia, with V-shaped dental arch
• Relative mandibular prognathism
• Dental anomalies (delayed or ectopic eruption, dental crowding)
Hands and Feet
• Osseous and/or cutaneous syndactyly, most com- monly with complete fusion of 2nd to 4th digits
• Cutaneous syndactyly of all toes with or without osseous syndactyly
• Proximal and middle symphalangism of digits 2 through 4
• Broad distal phalanges of thumbs, often fused with proximal phalanges
• Short, sometimes delta-shaped, proximal pha- langes of thumbs/great toes, positioned on ulnar/
fibular side of 1st metacarpal/metatarsal
• Carpal fusion (capitate-hamate)
A
Fig. 7.1. Patient 1, newborn. Note turricephaly, prominent forehead, flat face, depressed nasal bridge, shallow orbits, and complete fusion of digits 2–5, with common fingernail to dig- its 2–4
• Broad and trapezoidal distal phalanges of great toes, often fused with proximal phalanges
• Duplication of 1st metatarsal
• Progressive fusion, with age, of tarsals and metatarsals
• Hallux varus Extremities
• Radiohumeral synostosis
• Limitation of joint motion
• Short humerus, with flattened, subluxated humeral head
• Irregular glenoid fossa Spine
• Fused cervical vertebrae (usually at C5–6)
Apert Syndrome 594
Fig. 7.2. aPatient 2, 4 years. b Patient 3, 9 years. Note asymmet- rical, flat facies, shallow orbits, and hypertelorism. In a a devi- ated nasal septum is evident. In b strabismus and a ‘parrot’
nose are features a
b
Fig. 7.3. Patient 2, 4 years. The palate is narrow and V-shaped, with malpositioned teeth
Fig. 7.4 a, b. Patient 3, 9 years. a Note finger deformities and syndactyly in surgically repaired hands. b Note short and broad great toes, and syndactyly of toes 2–4
a
b
Bibliography
Anderson PJ, Hall CM, Evans RD, Hayward RD, Jones BM. The feet in Apert’s syndrome. J Pediatr Orthop 1999; 19: 504–7 Cohen MM.An etiologic and nosologic overview of craniosyn-
ostosis syndrome. Birth Defects Orig Art Ser 1973; 11:
137–89
Cohen MM, Kreiborg S. Hands and feet in the Apert syndrome.
Am J Med Genet 1995; 57: 82–96
Kreiborg A, Barr M, Cohen MM. Cervical spine in the Apert syndrome. Am J Med Genet 1992; 43: 704–8
Lajeunie E, Cameron R, El Ghouzzi V, de Parseval N, Journeau P, Gonzales M, Delezoide AL, Bonaventure J, Le Merrer M, Renier D. Clinical variability in patients with Apert’s syn- drome. J Neurosurg 1999; 90: 443–7
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Moloney DM, Slaney SF, Oldridge M, Wall SA, Sahlin P, Sten- man G, Wilkie AOM. Exclusive paternal origin of new mu- tations in Apert syndrome. Nat Genet 1996, 13: 48–53 Park WJ, Theda C, Maestri NE, Meyers GA, Fryburg JS,
Dufresne C, Cohen MM, Jabs EW. Analysis of phenotypic features and FGFR2 mutations in Apert syndrome. Am J Hum Genet 1995; 57: 321–8
Slaney SF, Oldridge M, Hurst JA, Morriss-Kay GM, Hall CM, Poole MD, Wilkie AO. Differential effects of FGFR2 muta- tions on syndactyly and cleft palate in Apert syndrome. Am J Hum Genet 1996; 58: 923–32
Apert Syndrome 595
A
Fig. 7.5. aPatient 4, newborn. (Courtesy of Dr. G. Beluffi, Uni- versity of Pavia, Italy). b Patient 5, newborn. (Reprinted, with permission, from Mastroiacovo et al. 1990.) The skull is brachycephalic, with decreased anteroposterior and increased
vertical diameter. The skull base is more vertical than normal, with short anterior fossa, and deep middle and posterior fossa.
The calvarium is thin. The maxillary bones are hypoplastic
a b
Apert Syndrome 596
Fig. 7.6. aPatient 4, newborn. The thumb is short and broad, with fusion of proximal and distal phalanges. There is sym- phalangism of proximal and middle finger phalanges, osseous syndactyly of finger 3 and 4, cutaneous syndactyly of fingers 2–5, and irregular shortening of metacarpals. (Courtesy of Dr. G. Beluffi, Pavia, Italy.) b Patient 5, 14 years. Surgical release of index fingers and secondary index finger clinodactyly. Note
osseous fusion of 4th and 5th metacarpals, 3rd and 4th finger middle phalanges, and capitate-hamate in the carpus. Also note delta-shaped proximal phalanx of thumb, with radial deviation on the right side (pollex varus), and proximal and middle symphalangism of fingers 2–5. (From the archive of Dr. P. Balestrazzi, Parma, Italy, with permission)
Fig. 7.7. Patient 4, newborn. Short and broad great toes, with deformed, fused proximal and distal phalanges. Only two pha- langes (proximal and distal) are seen in the 2nd to 5th toes.
Soft tissue syndactyly involves 2nd to 5th toes. (Courtesy of Dr.
G. Beluffi, Pavia, Italy)
a b
