Craniosynostoses

Molecular Genetics, Principles of Diagnosis, and Treatment

M. Muenke, W. Kress, H. Collmann, B. D. Solomon, M. Schmid

• Publisher: S. Karger
• Year: 2011
• Print ISBN:
  9783805595940
• eBook ISBN:
  9783805595957
• Topic: Medicina
• Subtopic: Medicina pediatrica

Craniosynostosis - the premature fusion of the cranial sutures of an infant's skull - is a challenging and complex condition that can occur as part of a syndrome or in isolation. In the last two decades increased knowledge about the structure and function of the human genome has enabled the discovery of the molecular etiologies of most forms of syndromic craniosynostosis, which in turn has allowed for the analysis of normal and abnormal sutural biology from the atomic to the population-based level. In parallel with the increase in basic biological understanding, advances in clinical diagnosis and treatment have been achieved including improved prenatal imaging technology and craniofacial surgical techniques as well as condition-specific care in specialized hospitals and clinical units. This book represents a comprehensive overview on the subject of craniosynostosis. Its 19 excellent chapters were written by the foremost authorities in the field for a wide range of readers. They cover topics including a historical review, basic biological and molecular studies, the various common and uncommon syndromes, nonsyndromic craniosynostoses, genetic testing, prenatal ultrasonography, and recent methods of neurosurgical and maxillofacial treatment. Both investigators at the bench and clinicians at the operating table will appreciate this timely book which will be the definitive volume on craniosynostosis for many years to come.

Chapter 11

Muenke M, Kress W, Collmann H, Solomon BD (eds): Craniosynostoses: Molecular Genetics, Principles of Diagnosis, and Treatment.
Monogr Hum Genet. Basel, Karger, 2011, vol 19, pp 119-142

______________________

Uncommon Craniosynostosis Syndromes: A Review of Thirteen Conditions

M.S. Raam^a,b · M. Muenke^a

^aMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md., ^bHHMI-NIH Research Scholars Program, Howard Hughes Medical Institute, Chevy Chase, Md., USA

______________________

Abstract

Uncommon craniosynostosis syndromes, while individually less well characterized than more common conditions such as Apert, Crouzon, Pfeiffer, Muenke, and Saethre-Chotzen syndromes, comprise a significant proportion of craniosynostosis cases when considered in sum. Thirteen of these rare syndromes are covered here with respect to nosology, associated clinical characteristics, and molecular genetics. They were selected for discussion in this chapter due to recent molecular advances therein that can significantly enhance clinicians’ ability to diagnose and counsel patients with these syndromes. The syndromes discussed here include Antley-Bixler syndrome, Baller-Gerold syndrome, Beare-Stevenson cutis gyrata syndrome, Bohring-Opitz syndrome, C (Opitz trigonocephaly) syndrome, Carpenter syndrome, Crouzon syndrome with acanthosis nigricans, Jackson-Weiss syndrome, Jacobsen syndrome, Loeys-Dietz syndrome type I, osteoglophonic dysplasia, P450 oxidoreductase deficiency, and Shprintzen-Goldberg syndrome.

Copyright © 2011 S. Karger AG, Basel

Syndromic craniosynostosis comprises approximately 15% of craniosynostosis cases, with well over 180 syndromes identified to date [1]. Although much attention is given to several well-characterized craniosynostosis syndromes, including Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, Muenke syndrome, and Saethre-Chotzen syndrome (see individual chapters on each in this volume), the vast majority of craniosynostosis syndromes are less well characterized and/or individually involve a comparatively small number of patients (see partial list in table 1). Despite these aspects of uncommon craniosynostosis syndromes, they comprise a significant proportion of craniosynostosis cases when considered in aggregate [2]. Additionally, the clinical issues observed in some uncommon syndromes differ from those encountered in the major syndromes: mental retardation and perinatal death, for instance, are seen more often in several uncommon syndromes, shifting focus away from simple surgical correction and creating a greater emphasis on prenatal diagnosis, psychomotor development, and genetic counseling [2]. Perhaps most importantly, description and delineation of uncommon craniosynostosis syndromes allow clinicians to better treat and counsel the significant numbers of families of patients with conditions that are not well understood.

Cohen Jr. and MacLean have provided a comprehensive discussion of the process of syndrome delineation, particularly with respect to craniosynostosis syndromes [2]. Based on whether or not a syndrome has an identifiable cause, it can be categorized as a syndrome of unknown genesis or as a syndrome of known genesis. Syndromes of unknown genesis can be further subdivided into syndromes with a provisionally unique pattern, in which a unique combination of anomalies has so far been observed in only 1 patient, and syndromes with a recurrent pattern, in which similar anomalies have been observed in 2 or more unrelated patients. Syndromes of known genesis can be further subdivided into those thought to have a monogenic cause, those with an identified chromosomal cause, those in which a specific enzymatic defect has been implicated, and those in which specific teratogens or environmental factors are causative. As of 1991, when 90 craniosynostosis syndromes had been identified, 40 syndromes were syndromes with mostly unidentified monogenic causes, 24 were syndromes of unknown genesis, 16 were syndromes with an identified chromosomal cause, and 4 were environmentally induced disorders [2].

Table 1. Partial list of uncommon craniosynostosis syndromes. Syndromes covered in this chapter are bolded and MIM numbers are provided wherever available. Although the text of this chapter covers relatively well-described syndromes for which underlying molecular bases are known, this list is provided as a starting point to demonstrate that the vast majority of the uncommon craniosynostosis syndromes are described in very few patients, do not clearly demonstrate Mendelian genetics, do not have a known underlying molecular basis, and/or are not clearly distinguishable from other syndromes. Better molecular characterization of patients and greater correlation between molecular findings and syndrome delineation can narrow this rather unwieldy list of syndromes to one that is more useful to clinicians and patients. (Adapted from Table 31-1, p. 385, Chapter 31, in [147] with permission from Oxford University Press, Inc.)

MIM number	Uncommon craniosynostosis syndromes
	Acrocephalospondylosyndactyly
201050	Acrocraniofacial dysostosis
%201550	Adducted thumbs (Christian) syndrome
#207410	Antley-Bixler syndrome
	Armendares syndrome
#218600	Baller-Gerold syndrome
	Baraitser syndrome
#123790	Beare-Stevenson cutis gyrata syndrome
	Berant syndrome
	Blair/Pakistan syndrome
#605039	Bohring-Opitz syndrome
#211750	C (Opitz trigonocephaly) syndrome
	CAP syndrome
	COH syndrome
	Calabro syndrome
302030	Calvarial hyperostosis
#201000	Carpenter syndrome
%605627	Cerebrooculonasal syndrome
	Cerebrotrichofacial syndrome
601853	Cerebellotrigeminal dermal dysplasia (Gómez-López-Hernández syndrome)
241519	Chitayat hypophosphatemia syndrome
112240	Cole-Carpenter syndrome
#218330, #613610	Cranioectodermal dysplasia
218350	Craniofacial dyssynostosis
	Craniofaciocervical osteoglyphic dysplasia
602558	Craniomicromelic syndrome
	Cranio-oculo-arthrogrypotic syndrome
123050	Craniorhiny
	Craniosyndactyly/intestinal atresia syndrome
603595	Craniosynostosis with ectopia lentis
#604757	Craniosynostosis, Boston type
%601222	Craniosynostosis, Philadelphia type
#612247	Crouzon syndrome with acanthosis nigricans
218670	Craniotelencephalic dysplasia
	Curry Carpenter-like syndrome
601707	Curry-Jones syndrome
%224690	Ear, patella, short stature (Meier-Gorlin) syndrome
200995	Elejalde syndrome
	Fontaine-Farriaux syndrome
#190440	Frydman trigonocephaly syndrome
	Fryns craniosynostosis syndrome
601370	Genoa syndrome
233500	Gorlin-Chaudhry-Moss syndrome
	Hall syndrome
#235510	Hennekam lymphangiectasia-lymphedema syndrome
#133701	Hereditary multiple exostoses, type II
	Herrmann syndrome
	Hersh syndrome
601379	Hunter-McAlpine syndrome
%241310	Hypomandibular faciocranial syndrome
	Idaho syndrome
#123150	Jackson-Weiss syndrome
#147791	Jacobsen syndrome
123155	Jones craniosynostosis/Dandy-Walker syndrome
	Kozlowski craniosynostosis syndrome
	Kreiborg/Pakistan syndrome
	Lampert syndrome
218649	Lin-Gettig syndrome
#609192, #610168	Loeys-Dietz syndrome, type I
	Lowry syndrome
600252	Lowry-MacLean syndrome
	Mehta syndrome
257920	Michels syndrome
%251230	Microcephaly-micromelia (Ives-Houston) syndrome
602361	Osteocraniostenosis/gracile bone dysplasia
#166250	Osteoglophonic dysplasia
#201750	P450 oxidoreductase deficiency
	Passos-Bueno craniosynostosis/cataracts syndrome
218450	Pfeiffer-type cardiocranial syndrome
	Pfeiffer-type dolichocephalosyndactyly
	Richieri-Costa overgrowth syndro...

Table of contents

• Cover Page
• Front Matter
• Craniosynostosis: A Historical Overview
• Discovery of MSX2 Mutation in Craniosynostosis: A Retrospective View
• Regulation of Calvarial Bone Growth by Molecules Involved in the Craniosynostoses
• Signal Transduction Pathways and Their Impairment in Syndromic Craniosynostosis
• The Molecular Bases for FGF Receptor Activation in Craniosynostosis and Dwarfism Syndromes
• Recurrent Germline Mutations in the FGFR2/3 Genes, High Mutation Frequency, Paternal Skewing and Age-Dependence
• Apert, Crouzon, and Pfeiffer Syndromes
• Muenke Syndrome
• Saethre-Chotzen Syndrome: Clinical and Molecular Genetic Aspects
• Craniofrontonasal Syndrome: Molecular Genetics, EFNB1 Mutations and the Concept of Cellular Interference
• Uncommon Craniosynostosis Syndromes: A Review of Thirteen Conditions
• Metopic Craniosynostosis Syndrome Due to Mutations in GLI3
• Craniosynostosis and Chromosomal Alterations
• Nonsyndromic Craniosynostoses
• Molecular Genetic Testing of Patients with Craniosynostosis
• Prenatal Sonographic Diagnosis of Craniosynostosis
• Clinical Approach to Craniosynostosis
• Imaging Studies and Neurosurgical Treatment
• Maxillofacial Examination and Treatment
• Author Index
• Subject Index