ALTERNATE NAMES

Brain Malformations-Musculoskeletal Abnormalities-Facial Dysmorphism-Intellectual Disability Syndrome; ZTTK Syndrome

DESCRIPTION

Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare genetic disorder characterized by a combination of neurological, developmental, and physical abnormalities. ZTTK syndrome is caused by a change in the SON gene at conception. Most individuals with ZTTK syndrome have a new (de novo) variant in the SON gene that was not inherited from either biological parent. This condition typically affects multiple body systems; however, it can affect each individual differently depending on where the change is located on the SON gene.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: ZTTK syndrome is diagnosed by:

• •

  Clinical examination;

• •

  A detailed patient and family history;

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  Magnetic resonance imaging (MRI) of the brain;

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  Electroencephalogram (EEG); and

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  Whole exome sequencing (WES).

Molecular genetic testing such as chromosomal microarray analysis (CMA), fluorescent in situ hybridization (FISH), and cytogenetic analysis (karyotyping) for variants of the SON gene can confirm the diagnosis.

Physical findings: How individuals are affected by ZTTK syndrome will vary based on where changes occurred on the SON gene. Some common signs and symptoms of this condition may include:

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  Developmental delay;

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  Intellectual disability;

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  Brain malformations;

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  Unique facial features (facial asymmetry, midface retraction, deep-set eyes, low set ears);

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  Muscle abnormalities (low muscle tone, contractures or loose joints);

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  Spinal curvature (scoliosis, kyphosis);

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  Eye abnormalities (misaligned eyes, vision loss); and

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  Short stature.

ICD-9: 759.0

ICD-10: Q87.8

PROGRESSION

ZTTK syndrome typically progresses with a noticeable developmental delay, where intellectual disability increases with age, often presenting with delayed motor skills, language acquisition, and cognitive development, alongside potential brain abnormalities like abnormal gyral patterns and white matter issues. Symptoms of ZTTK syndrome may start to appear as a newborn. However, some symptoms can begin at any age. Seizures may also develop between the ages of 1 and 6 years old in many patients, while other symptoms like facial dysmorphisms and musculoskeletal abnormalities may become more apparent over time.

TREATMENT

There is no cure for ZTTK syndrome. Treatment is supportive and based on individual symptoms. A specialist care team may include genetics/genetic counseling, neurology, psychiatry, cardiology, nephrology, ophthalmology, audiology, immunology, orthopedics, and gastroenterology. Affected children should have imaging to screen for kidney and heart abnormalities. Imaging of the brain may include MRI to identify structural brain differences and EEG if seizures are suspected. Growth, feeding and development should be monitored.

Supportive therapies such as speech, occupational, and physical therapies may be helpful, and school aged children may benefit from accommodations such as an individualized education plan (IEP). Genetic counseling is recommended for affected children and their families.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment; and

• •

  Genetic testing confirming the presence of SON gene mutations.

Suggested Listings for Evaluation:

Meets

101.18

101.24

102.02

102.03

102.04

102.10

104.06

110.08 B

111.02 A or B

111.09

112.02

112.05

112.11

112.14

Equals