eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Apert Syndrome: Differential Diagnoses & Workup

Author: Harold Chen, MD, MS, FAAP, FACMG, Professor, Departments of Pediatrics, Obstetrics and Gynecology, and Pathology, Director of Genetic Laboratory Services, Louisiana State University Medical Center
Contributor Information and Disclosures

Updated: Sep 2, 2009

Differential Diagnoses

Crouzon Syndrome

Other Problems to Be Considered

Mutations of the human FGFR s have also been identified as the cause of other craniosynostosis syndromes, including Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome, Beare-Stevenson syndrome, cutis gyrata, Antley-Bixler syndrome, and Muenke syndrome, as well as skeletal dysplasias such as achondroplasia and thanatophoric dysplasia.10,11,12,13,14,15,16  

  • Beare-Stevenson syndrome (OMIM 123790): Patients present with mental retardation and associated cutaneous disorders, including cutis gyrata and acanthosis nigricans. Patients with Beare-Stevenson syndrome may have FGFR2 mutations.
  • Carpenter syndrome (OMIM 201000): This condition is autosomal recessive. Patients present with a peculiar face, absence of osseous fusion of hand bones, and preaxial polydactyly of hands, feet, or both.
  • FGFR3 -associated coronal synostosis syndrome: Patients present with variable clinical presentation overlapping with Pfeiffer, Jackson-Weiss, or Saethre-Chotzen syndrome phenotypes. Some individuals with a disease-causing mutation may have no clinical problems.
  • Jackson-Weiss syndrome (OMIM 123150): Patients present with enlarged or broad great toes with varus deviation and tarsal or metatarsal fusion, lack of thumb abnormalities, and craniofacial features, suggesting Pfeiffer syndrome. Patients may have FGFR2 mutations.
  • Pfeiffer syndrome (OMIM 101600): Patients present with hand and foot abnormalities characterized by broad thumbs and halluces with occasional cutaneous syndactyly. They also exhibit mild cranial deformities and lack of osseous fusion of the phalanges. Approximately 67% of patients with Pfeiffer syndrome have identifiable mutations in FGFR1 and FGFR2.
  • Saethre-Chotzen syndrome (OMIM 101400): Patients exhibit characteristic facies, relatively mild cranial deformity, and lack of osseous fusion of the hand bones. Approximately 75% of patients with Saethre-Chotzen syndrome have identifiable mutations in the TWIST gene.

Workup

Laboratory Studies

  • Molecular analysis of Apert syndrome
    • The molecular mechanism is exquisitely specific with a narrow mutational spectrum.
    • More than 98% of cases are caused by specific missense substitution mutations, involving adjacent amino acids (Ser252Trp, Ser252Phe, or Pro253Arg) in exon 7 of FGFR2.
    • The remaining cases are due to Alu-element insertion mutations in or near exon 9.

Imaging Studies

  • Skull radiography
    • Skull radiography can be performed to evaluate for craniostenosis, which usually involves coronal sutures and maxillary hypoplasia.
    • Abnormalities include sclerosis of suture line, bony bridging and beaking along the suture line, an indistinct suture line, turribrachycephaly, shallow orbits, and hypoplastic maxillae.
  • Spinal radiography
    • Spinal fusions, most commonly at the levels of C3-4 and C5-6, appear to be progressive and occur at the site of subtle congenital anomalies. They may not be apparent as congenital features.
    • Small-sized vertebral body and reduced intervertebral disc space are indicators of subsequent bony fusion.
  • Limb radiography: Radiographs of the limbs depict multiple epiphyseal dysplasia, short humeri, and glenoid dysplasia.
  • Hand radiography
    • Radiography of the hands can be performed to evaluate for cutaneous and osseous syndactyly.
    • The characteristic finding is complete syndactyly involving the second and fifth digits (mitten hands).
    • Multiple progressive synostosis involves distal phalanges, proximal fourth and fifth metacarpals, capitate, and hamate.
    • Symphalangism of interphalangeal joints is progressive.
    • Radiography of the distal phalanx reveals shortened and radial deviation.
    • Radiography of the proximal phalanx of the thumbs reveals delta-shaped deformity.
  • Foot radiography
    • Radiography of the feet can be performed to evaluate for cutaneous and osseous syndactyly. The characteristic finding is complete syndactyly involving the second and fifth digits (sock feet).
    • Fusion of tarsal bones, metatarsophalangeal and interphalangeal joints, and adjacent metatarsals
    • Delta-shaped proximal phalanx of the first toes
    • Occasional partial or complete duplication of the proximal phalanx of the great toes and first metatarsals
  • CT scanning
    • CT with comparative 3-dimensional reconstruction analysis of the calvaria and cranial bases has become the most useful radiological examination in identifying skull shape and presence or absence of involved sutures.
    • CT can precisely reveal the pathological anatomy and permit specific operative planning.
  • MRI
    • MRI reveals the anatomy of the soft-tissue structures and associated brain abnormalities (ie, nonprogressive ventriculomegaly; hydrocephalus; complete or partial absence of the septum pellucidum; absence of septal leaflets; and thinning, deficiency, or agenesis of the corpus callosum).17,18
    • MRI can also reveal spatial arrangement of the bones.

Other Tests

  • Psychometric evaluation
  • Hearing assessment

More on Apert Syndrome

Overview: Apert Syndrome
Differential Diagnoses & Workup: Apert Syndrome
Treatment & Medication: Apert Syndrome
Follow-up: Apert Syndrome
Multimedia: Apert Syndrome
References
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References

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Further Reading

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Keywords

acrocephalosyndactyly Apert type, acrocephalosyndactyly type I, type I acrocephalosyndactyly, Apert's syndrome, typical acrocephalosyndactyly, autosomal dominant disorder, craniosynostosis, craniofacial anomalies, symmetrical syndactyly, cutaneous and bony fusion of hands and feet, Apert syndrome, craniostenosis, sleep apnea, cor pulmonale, stridor, conjunctivitis, keratitis, acrocephaly, brachycephaly, turribrachycephaly, flat occiput, down-slanting palpebral fissures, hypertelorism, shallow orbits, proptosis, exophthalmos, strabismus, amblyopia, optic atrophy, luxation of the eye globes, keratoconus, ectopic lentis, congenital glaucoma

crowded upper teeth, malocclusion, delayed dentition, ectopic eruption, shovel-shaped incisors, supernumerary teeth, V-shaped maxillary dental arch, bulging alveolar ridges, dentitio tarda, partial eruption, idiopathic root resorption, megalencephaly, agenesis of the corpus callosum, malformed limbic structures, variable ventriculomegaly, encephalocele, gyral abnormalities, hypoplastic cerebral white matter, pyramidal tract abnormalities, heterotopic gray matter, progressive hydrocephalus, atrial septal defect, patent ductus arteriosus, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot, treatment, diagnosis

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Contributor Information and Disclosures

Author

Harold Chen, MD, MS, FAAP, FACMG, Professor, Departments of Pediatrics, Obstetrics and Gynecology, and Pathology, Director of Genetic Laboratory Services, Louisiana State University Medical Center
Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Human Genetics, and Teratology Society
Disclosure: Nothing to disclose.

Medical Editor

James Bowman, MD, Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago
James Bowman, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Pathology, American Society of Human Genetics, Central Society for Clinical Research, and College of American Pathologists
Disclosure: Nothing to disclose.

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Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Hagop Youssoufian, MD, MSc, Vice President of Clinical Research, ImClone Systems Incorporated
Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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