Cassidy and Allanson's Management of Genetic Syndromes

John C. Carey, Suzanne B. Cassidy, Agatino Battaglia, David Viskochil, John C. Carey, Suzanne B. Cassidy, Agatino Battaglia, David Viskochil

• Publisher: Wiley-Blackwell
• Year: 2020
• ISBN:
  9781119432654
• Edition: 4
• Topic: Biological Sciences
• Subtopic: Genetics & Genomics
• Index: Biological Sciences

MANAGEMENT OF GENETIC SYNDROMES

THE MOST RECENT UPDATE TO ONE OF THE MOST ESSENTIAL REFERENCES ON MEDICAL GENETICS

Cassidy and Allanson's Management of Genetic Syndromes, Fourth Edition is the latest version of a classic text in medical genetics. With newly covered disorders and cutting-edge, up-to-date information, this resource remains the most crucial reference on the management of genetic syndromes in the field of medical genetics for students, clinicians, caregivers, and researchers. The fourth edition includes current information on the identification of genetic syndromes (including newly developed diagnostic criteria), the genetic basis (including diagnostic testing), and the routine care and management for more than 60 genetic disorders.

Written by experts, each chapter includes sections on:

• Incidence
• Diagnostic criteria
• Etiology, pathogenesis and genetics
• Diagnostic testing
• Differential diagnosis
• Manifestations and Management (by system)

The book focuses on genetic syndromes, primarily those involving developmental disabilities and congenital defects. The chapter sections dealing with Manifestations and Management represents the centerpiece of each entry and is unmatched by other genetic syndrome references.

Management of Genetic Syndromes is perfect for medical geneticists, genetic counselors, primary care physicians and all healthcare professionals seeking to stay current on the routine care and management of individuals with genetic disorders.

1
AARSKOG SYNDROME

Roger E. Stevenson

Curry Chair in Genetic Therapeutics, Greenwood Genetic Center, Greenwood, South Carolina, USA

INTRODUCTION

Aarskog syndrome is one of the most clinically distinctive phenotypes among the hereditary syndromes. Manifestations in the facial morphology, skeleton, and genitalia comprise a clinically useful diagnostic triad, present from birth. The condition was first described in a Norwegian family by the pediatrician Dagfinn Aarskog in 1970 and in an American family by the geneticist Charles Scott in 1971. Aarskog syndrome is an X‐linked condition with fully expressed manifestations in males and subtle findings in many carrier females. The causative gene, FGD1, located at Xp11.22 was identified in 1994 (Pasteris et al. 1994).

Although the condition has been given the more descriptive names of facial‐genital‐digital syndrome and faciogenital dysplasia, the designations Aarskog syndrome and Aarskog–Scott syndrome have retained greatest favor.

Incidence

Over 250 affected individuals with Aarskog syndrome have been reported, providing a rich descriptive literature and precluding the reporting of most currently identified cases (Aarskog, 1970; Scott 1971; Furukawa et al. 1972; Porteous and Goudie 1991; Fryns 1992; Teebi et al. 1993; Fernandez et al. 1994; Stevenson et al. 1994; Orrico et al. 2004, 2005, 2007, 2015; Shalev et al. 2006; Bottani et al. 2007; Pérez‐Coria et al. 2015; Griffin et al. 2016). Many multigenerational pedigrees have been identified because of the X‐linked inheritance pattern, the presence of distinctive external manifestations, and the absence of lethal manifestations. Aarskog syndrome has been reported worldwide and from most ethnic and racial groups. There does not appear to be an increased rate in any subpopulation. Among those clinically diagnosed, only about 20% are found to have FGD1 mutations, suggesting overdiagnosis or genetic heterogeneity among these cases.

The wide recognition and large number of ascertained cases notwithstanding, a reliable prevalence for Aarskog syndrome is not known. An estimate of 1/25,000 live births has been made (Orrico et al. 2015). Subtle manifestations permit many, perhaps most, cases to go undiagnosed.

Lifespan is said to be normal, but this too has not been documented by systematic study. Survival into the eighth decade is found within the reported pedigrees.

Diagnostic Criteria

The diagnosis of Aarskog syndrome is based on clinical findings. In most cases, the pattern of craniofacial, skeletal and genital manifestations is sufficient to make the diagnosis (Table 1.1). Identification of an X‐linked pattern of inheritance and the presence of subtle findings in carrier females assist in familial cases. A responsible gene has been identified and testing for sequencing variants and deletions/duplications is currently available in many diagnostic laboratories.

Manifestations of Aarskog syndrome are present from birth. Head size is usually normal, but may appear large in relation to the face and the body. The facial appearance is distinctive and in most individuals is diagnostic (Figure 1.1). Changes are present in the upper, middle, and lower portion of the face. Increased width of the forehead, widow’s peak, ocular hypertelorism, down‐slanted palpebral fissures, and blepharoptosis are the major features of the upper face. A short nose with anteverted nares and small simply formed ears that may protrude are the major features of the midface. Ears often have a broad insertion. The midface may be hypoplastic, but this is rarely of sufficient degree to dominate the appearance of the face. The mouth is wide and...