Craniosynostosis syndromes.pptx,,,,,,,,,,,

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1. Craniosynostosis syndromes By Dr mandefro.A ( R1)

2. INTRODUCTION Craniosynostosis , defined as premature fusion or growth arrest at one or more of the cranial sutures, most commonly occurs sporadically as an isolated defect

3. Syndromes most frequently associated with craniosynostosis include Apert , Crouzon , Pfeiffer, Carpenter , and Saethre-Chotzen .

4. Syndromic craniosynostoses are often sporadic and are the result of de novo autosomal dominant mutations involving fibroblast growth factor receptors (FGFRs) and TWIST genes

5. Common features of these conditions are: skull-base abnormalities, midface hypoplasia , and limb anomalies

6. APERT SYNDROME ( acrocephalosyndactyly type I)  is an autosomal dominant disorder that occurs in 6 to 15.5 out of 1 million livebirths . Most cases are sporadic . Mutations in the gene encoding fibroblast growth factor receptor 2 ( FGFR2 ), located on chromosome 10, account for almost all known cases.

7. Clinical features bicoronal synostosis and maxillary hypoplasia , that cause a flat, recessed forehead and flat midface protruding eyes ( exorbitism ), widely separated orbits ( hypertelorism ), antimongoloid or laterally downsloping slant. Low-set ears are often accompanied by an abnormally small, flat nasal structure with a bulbous tip

8. The palate is often highly arched and may be associated with clefting in 1/3 of patients . The maxillary dental arch is frequently V shaped. A class 3 malocclusion ( underbite ) is considered a nearly universal finding

9. Strabismus is a frequent finding in Apert syndrome, as is hearing loss resulting from persistent middle-ear effusion . The small, malformed pharynx and hypoplastic midface may result in airway compromise. Severe acne vulgaris develops in 70 percent of patients with Apert syndrome and frequently involves the extremities

10. Syndactyly is a characteristic feature of Apert syndrome that permits distinction from other similar syndromes Patients with Apert syndrome typically have a complex syndactyly known as mitten hand , in which the index, middle, ring, and fifth fingers share fused bone and soft tissue components with a common nail bed. The thumb is often relatively well formed and mobile. A similar syndactyly is frequently demonstrated in the feet 

11.   megalencephaly  malformations of the corpus callosum and limbic structures , gyral abnormalities, hypoplastic white matter, and heterotopic gray matter . Most patients had ventriculomegaly , resulting from distortion imposed upon a large brain within a misshapen skull ; however, progressive hydrocephalus occurred in only 10 percent of cases

12. Cardiovascular ( atrial septal defect, ventricular septal defect, patent foramen ovale , overriding aorta) and genitourinary ( hydronephrosis , cryptorchidism ) anomalies occurred in 10 and 9.6 percent of cases, respectively. I

13. CROUZON SYNDROME  (craniofacial dysostosis type I)  is autosomal dominant and occurs at a frequency of 16 in 1 million livebirths . predominantly caused by mutations in fibroblast growth factor receptor 2 ( FGFR2) , although fibroblast growth factor receptor 3  (FGFR3)  mutations have been identified in individuals with Crouzon syndrome and acanthosis nigricans .

14. Clinical features tall, flattened forehead (secondary to bicoronal synostosis ), proptosis , a beaked nose, and midface hypoplasia . The degree of facial deformity is milder than that of Apert syndrome , and cleft palate is rare. Also in contrast to Apert syndrome, patients with Crouzon syndrome typically have structurally normal hands and feet, as well as normal intelligence.

15. Cervical spine abnormalities occur in up to one-third of patients and must be thoroughly evaluated before surgical correction of craniosynostosis . The surgical treatment is similar in timing and technique to that used in Apert syndrome

16. PFEIFFER SYNDROME  (Pfeiffer-type acrocephalosyndactyly type V)  is the result of an autosomal dominant genetic defect.  is most commonly associated with mutations in fibroblast growth factor receptor 1  (FGFR1)  and fibroblast growth factor receptor 2  (FGFR2) .

17. clinical features variable degrees of craniosynostosis and midface hypoplasia . Broad thumbs and abnormally wide great toes are often paired with partial syndactyly of the second and third fingers, as well as second, third, and fourth toes. The presence and extent of syndactyly are variable. Skeletal ( eg , radiohumeral synostosis of the elbow), central nervous system (CNS; eg , hydrocephalus), and gastrointestinal abnormalities ( eg , imperforate anus) also frequently occur

18.   Pfeiffer syndrome is classified into three subtype : type 1 : symmetric bicoronal craniosynostosis , variable syndactyly , broad thumbs,  widened great toes . Intelligence is normal or near normal. Types 2 and 3: have a more severe phenotypic expression

19. usual bicoronal craniosynostosis , multiple other sutures are frequently involved. Types 2 and 3 are similar in clinical features and outcome; however, they may be differentiated by the cloverleaf skull anomaly, which is only present in type 2 .

20. Type 2 Pfeiffer syndrome is also characterized by severe ocular proptosis , ankylosis of the elbows, broad thumbs and great toes, as well as visceral anomalies . There is severe CNS involvement, most often manifest as hydrocephalus, with poor prognosis and frequent early death. To date, all documented cases of type 2 have been sporadic

21. Type 3 Pfeiffer syndrome is similar to type 2; however, the cloverleaf skull deformity is absent . Severe ocular proptosis is present, and patients often have a markedly shorter anterior cranial base. Severe neurologic defects are common, and patients typically die early. As with type 2 Pfeiffer syndrome, all documented cases have occurred sporadically.

22. CARPENTER SYNDROME also known as acrocephalopolysyndactyly II is a rare autosomal recessive disorder. It is associated with mutations in  RAB23  (RAS-associated protein), a guanosine triphosphate hydrolase ( GTPase ) involved in intracellular membrane trafficking regulation.

23. brachycephaly with concurrent coronal, sagittal , and lambdoid craniosynostosis . The supraorbital ridges are shallow, the nasal bridge is flat, and the lateral canthi are displaced laterally with or without inner canthal folds. Other craniofacial features include a hypoplastic mandible and/or maxilla, low-set and malformed ears, and a narrow, high-arched palate.

24. frequently affected by preaxial polydactyly (supernumerary digits of the medial ray). Common findings include brachydactyly (short digits) of the hands with clinodactyly (curved fingers), partial syndactyly , and camptodactyly (permanent flexion of the digit).

25. Cardiovascular anomalies are common in patients with Carpenter syndrome. Up to 50 percent demonstrate ventricular or atrial septal defect, patent ductus arteriosus , pulmonic stenosis , tetralogy of Fallot , or transposition of the great arteries. Hypogonadism and omphalocele also have been linked to Carpenter syndrome. In addition , patients tend to be obese and moderately mentally impaired .

26. SAETHRE-CHOTZEN SYNDROME known as acrocephalosyndactyly type III  is an autosomal dominant disorder

27. Cont….. craniosynostosis of coronal, lambdoid , and/or  metopic sutures. The characteristic facial appearance includes a towering ( turricephalic ) forehead, low-set hairline , facial asymmetry with septal deviation, and ptosis of the upper eyelids. Cutaneous syndactyly , usually partial, frequently occurs and involves the second and third fingers and/or the third and fourth toes. Most patients have normal intelligence

28. SUMMARY Craniofacial features of Apert syndrome ( acrocephalosyndactyly type I) include bicoronal synostosis , maxillary hypoplasia , protruding eyes with a laterally downsloping slant, hypertelorism , low-set ears, and high-arched palate. Additional features may include intellectual disability, strabismus, hearing loss, severe acne, and syndactyly of the hands and feet.

29. Craniofacial features of Crouzon syndrome (craniofacial dysostosis type I) include; bicoronal synostosis , proptosis , and midface hypoplasia . The hands are typically normal, as is intelligence .

30. Craniofacial features of Pfeiffer syndrome ( acrocephalosyndactyly type V) include variable degrees of craniosynostosis , midface hypoplasia , and proptosis . The presence and extent of syndactyly is variable. Additional manifestations may include broad thumbs and great toes, radiohumeral synostosis , hydrocephalus, and imperforate anus. Type 1 is mild. Types 2 and 3 are associated with severe neurologic defects that lead to early death.

31. Craniofacial features of Carpenter syndrome ( acrocephalopolysyndactyly type II) include; coronal, sagittal , and lambdoid craniosynostosis ; shallow supraorbital ridges; flat nasal bridge; laterally displaced lateral canthi ; hypoplastic mandible and/or maxilla; low-set and malformed ears; and narrow , high-arched palate. Additional features may include abnormalities of the digits (supernumerary, short, curved, permanent flexion), cardiovascular anomalies, hypogonadism , omphalocele , and obesity .

32. Craniofacial features of Saethre-Chotzen syndrome ( acrocephalosyndactyly type III) include ; craniosynostosis of coronal, lambdoid , and/or  metopic sutures, towering ( turricephalic ) forehead, low-set hairline, facial asymmetry with septal deviation, and ptosis . Many patients often have partial syndactyly

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