Emanuel syndrome

Overview

Emanuel syndrome is a rare chromosomal disorder characterized by multiple congenital anomalies and significant developmental delays. It results from an extra derivative chromosome 22, often due to a parental balanced translocation between chromosomes 11 and 22. The syndrome was first described by Dr. Beverly Emanuel and colleagues and is also known as derivative 22 syndrome. Infants with Emanuel syndrome typically present with distinct facial features, intellectual disability, and various structural abnormalities affecting the heart, kidneys, and other organs.

Causes

Emanuel syndrome is caused by the presence of a supernumerary derivative chromosome 22, usually denoted as der(22)t(11;22). This occurs when a child inherits an unbalanced translocation from a parent who carries a balanced translocation between chromosomes 11 and 22. The extra genetic material disrupts normal development and leads to the clinical features of the syndrome.

Inheritance follows a chromosomal translocation mechanism, and most parents of affected children are asymptomatic balanced translocation carriers. The risk of recurrence is higher in families where one parent is a known carrier.

Symptoms

The symptoms and severity of Emanuel syndrome vary but typically include:

• Craniofacial features: Prominent forehead, large low-set ears, long philtrum, flat nasal bridge, small jaw (micrognathia), and cleft or high-arched palate

• Developmental delays: Severe delays in speech, motor skills, and cognitive abilities

• Hypotonia: Low muscle tone from infancy

• Microcephaly: Abnormally small head size

• Failure to thrive: Feeding difficulties and poor growth in infancy

• Congenital heart defects: Including atrial septal defect (ASD) or ventricular septal defect (VSD)

• Genitourinary anomalies: Kidney malformations, undescended testes, or ambiguous genitalia

• Hernias: Inguinal or umbilical hernias are common

• Hearing and vision problems: Including hearing loss and strabismus (crossed eyes)

• Seizures: May develop in some individuals

Diagnosis

Diagnosis of Emanuel syndrome is confirmed through chromosomal analysis. Key diagnostic steps include:

• Karyotyping: Detects the presence of the supernumerary derivative chromosome 22

• Fluorescence in situ hybridization (FISH): Used to identify specific chromosomal rearrangements

• Chromosomal microarray analysis: Provides a detailed view of the extra genetic material

• Parental karyotyping: To determine whether one parent carries the balanced t(11;22) translocation

• Physical examination and imaging: To assess for organ abnormalities and developmental milestones

Treatment

There is no cure for Emanuel syndrome. Treatment is supportive and focuses on managing individual symptoms through a multidisciplinary approach. Common management strategies include:

• Early intervention programs: Including physical, occupational, and speech therapy

• Feeding support: May include feeding tubes in infancy for severe failure to thrive

• Surgical correction: For cleft palate, heart defects, or hernias

• Seizure management: Using antiepileptic medications if seizures occur

• Educational support: Special education services tailored to developmental level

• Routine monitoring: Hearing, vision, cardiac, and renal evaluations

• Genetic counseling: For affected families to understand recurrence risk and family planning options

Prognosis

The prognosis for children with Emanuel syndrome varies depending on the severity of their symptoms and associated organ malformations. Most individuals experience significant developmental delays and intellectual disability. Some may be nonverbal or require assistance with daily activities throughout life. Life expectancy can be reduced, particularly in cases with severe heart or kidney anomalies, though many children live into adolescence or adulthood with comprehensive medical care and support.