Dysmorphic Infant: Terminology and Evaluation

Terminology

• Malformations arise from inherent changes in genetic mechanisms
• Deformations: Structural flaws are caused by mechanical forces
• Dysplasia: The atypical growth or development of tissues, organs, or cells
• Disruptions: Physical forces that interfere with or distort fetal tissue
• Syndromes: A collection of malformations that occur in a recognizable pattern with a known genetic cause
• Associations: Well-known co-occurring malformations without a recognized genetic cause

Evaluation of a Dysmorphic Infant

• History: Gather pregnancy details, including miscarriages, stillbirths, drug exposure, and complications
• Gestational Age: Note the gestational age to assess for prematurity
• Family History: Helps identify potential diagnoses based on genetic conditions
• Parental Factors: Consider parental habits and work environments for exposures
• Physical Exam: Evaluate growth parameters to identify any abnormalities in development
• Skeletal Dysplasia and other findings are evaluated through physical exam

Diagnostic Tools

• X-ray: Useful for skeletal surveys to detect skeletal dysplasia
• MRI: Used for diagnostic evaluation of neurologic symptoms and deep tissue evaluation
• CT Scan: Assesses skull sutures in suspected cases of craniosynostosis
• Ultrasound: Evaluates the brain and spine in neonates and images abdominal organs for malformations

Chromosomal Disorders: Abnormal Number

Trisomy 21 (Down Syndrome)

• Newborn: Infants may experience feeding problems, constipation, prolonged jaundice, and blood count abnormalities
• Childhood: Potential issues include thyroid dysfunction, vision and hearing impairments, obstructive sleep apnea, celiac disease, atlanto-occipital instability, varying degrees of cognitive disability, and a higher risk of certain blood disorders (transient myeloproliferative disorder and leukemia)
• Clinical Findings: Characteristic facial features include upslanted eyes, a flat nasal bridge, epicanthal folds, midface hypoplasia, a flattened occiput, minor limb abnormalities, and overall hypotonia
• Heart Issues: About 50% have congenital heart disease, like endocardial cushion defects or other septal defects
• GI anomalies: 15% have esophageal and duodenal atresias
• Genetic Counseling: Trisomy results from nondisjunction, with risk increasing with maternal age and a recurrence risk of 1 per 100 plus age-specific maternal risk; risks are increased if the child has a trisomy resulting from a translocation and the parent has an abnormal karyotype

Sex Chromosome Abnormalities

• Turner Syndrome (Monosomy X): Often leads to spontaneous abortion
• Diagnosis: Presents with short stature and primary amenorrhea. Associated with coarctation of the aorta and genitourinary malformations. Normal IQ, but learning disabilities are common
• Newborn: Signs include short stature, webbed neck, edema of hands and feet, and triangular faces
• Older Girls: Features include short stature, a broad chest with wide nipples, mixed hearing loss, horseshoe kidneys, streak ovaries, amenorrhea, lack of secondary sex characteristics, and infertility
• Klinefelter Syndrome (XXY): Does not lead to spontaneous abortion
• Diagnosis: Tall stature with eunuchoid body habitus, small testes, and male infertility. Variable learning and cognitive difficulties
• Diagnosis is rarely made before puberty
• Clinical Findings: Small testicles (normal genitalia otherwise), gynecomastia, reduced body and facial hair, tall stature, eunuchoid build, decreased muscle mass, borderline to normal IQ, and low testosterone

Chromosomal Abnormalities: Abnormal Structure

• Newborns often present with multiple congenital anomalies

Mendelian Disorders

• Marfan Syndrome:
• Diagnosis: Based on skeletal abnormalities, lens dislocation, aortic root dilation, dural ectasia, and possibly a positive family history
• Clinical Findings: Ghent criteria are used for diagnosis

Noonan Syndrome

• Characteristics: Includes short stature, congenital heart disease, mild dysmorphism, and feeding problems
• Heart Issues: Commonly associated with pulmonary stenosis and hypertrophic cardiomyopathy
• Developmental Delays: Mild delays in gross motor skills and speech are frequently observed

Nonmendelian Disorders

• Prader-Willi Syndrome (PWS): Caused by a lack of paternal expression of imprinted genes
• Clinical Characteristics: Severe hypotonia in infancy, poor feeding that progresses through multiple nutritional stages, and later, hyperphagia (inability to feel full)
• Angelman Syndrome:
• Presents as: developmental delay, greatly impacting expressive language, intellectual disability, seizures, movement disorders, sleep disturbances, gastrointestinal concerns, and stereotypical behaviors including excitable and happy demeanor

Disorders Associated with Anticipation

• Fragile X Syndrome: The most prevalent cause of intellectual disability in males (X-linked)
• Clinical Presentation: Features include hyperextensible joints, mitral valve prolapse, aortic root dilation, and autism spectrum disorder

Disorders of Multifactorial Inheritance

• Cleft Lip/Palate: Separate genetic causes for cleft lip (with or without cleft palate) and isolated cleft palate
• Findings: A cleft lip can be unilateral or bilateral, complete or incomplete, and can affect the entire palate or parts of it
• Isolated Cleft Palate: Impacts the soft palate or both soft and hard palates, V or U-shaped
• Pierre Robin Sequence: Cleft palate with micrognathia and glossoptosis, leading to respiratory and feeding problems

Types of Clefts

• Cleft Lip
• Cleft Palate
• Cleft Lip and Cleft Palate

Perinatal Genetics

• Fetal Alcohol Syndrome:
• Results in: short stature, poor head growth, developmental delay, midface hypoplasia, poorly developed philtrum, thin upper lip, narrow palpebral fissures, and a short nose with upturned nostrils