Diagnostic Criteria

This chapter focuses on classic and atypical Schinzel-Giedion syndrome (SGS). Before pathogenic variants within SETBP1 were identified to cause classic Schinzel-Giedion syndrome (SGS), clinical diagnostic criteria for classic SGS were proposed .

Suggestive Findings

Schinzel-Giedion syndrome (SGS) should be considered in a proband with the following clinical findings and family history.

Clinical findings

• Moderate-to-profound developmental delay (DD) or intellectual disability (ID)

• Facial features include a prominent forehead, midface retrusion, and bitemporal narrowing with or without other characteristics features . Although facial features are typical in both classic and atypical SGS, the facial features in individuals with atypical SGS are not as coarse.

Source: GeneReviews — "Schinzel-Giedion Syndrome"

Differential Diagnosis

The phenotypic features associated with classic Schinzel-Giedion syndrome (SGS) are often sufficient to diagnose this condition clinically. However, in individuals with findings in the moderate end of the spectrum of classic SGS (e.g., less apparent dysmorphisms, no hydronephrosis or other congenital anomalies and/or epilepsy) or atypical SGS, the following monogenic disorders , chromosomal anomalies, and teratogenic conditions may be considered in the differential diagnosis.

Table 4.

Selected Monogenic Disorders in the Differential Diagnosis of Classic and Atypical Schinzel-Giedion Syndrome

Gene | Disorder | MOI | Features of Disorder

Overlapping w/SGS | Distinguishing from SGS

ARSB

ARSK

GALNS

GLB1

GNS

GUSB

HGSNAT

HYAL1

IDS

IDUA

NAGLU

SGSH

Source: GeneReviews — "Schinzel-Giedion Syndrome"

Management Guidelines

No clinical practice guidelines for classic or atypical Schinzel-Giedion syndrome (SGS) have been published. The recommendations in this section reflect the authors' experience in the management of individuals with SGS. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with classic or atypical SGS, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 5. Schinzel-Giedion Syndrome: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "Schinzel-Giedion Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 7.

Schinzel-Giedion syndrome: Recommended Surveillance

System/Concern | Evaluation | Frequency

Feeding

| • Measurement of growth parameters (weight, height, head circumference)

• Eval of nutritional status safety of oral intake incl swallowing problems/ dysphagia

| At each visit

Gastrointestinal

| • Monitor for constipation.

• Monitor gastroesophageal reflux disease perform additional GI assessments if needed.

• In case of chronic vomiting, consider gastroparesis.

Respiratory

| Monitor for evidence of aspiration, breathing problems due to excess mucus production, respiratory insufficiency.

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new manifestations such as seizures, changes in tone, movement disorders.

• Consider brain /or spine MRI depending on clinical changes (incl changes in mood, irritability, alertness).

CAKUT

| Per treating urologist | • Frequency based on clinical findings

• Consider bladder atony when urinary tract infections are frequent persistent.

Per treating nephrologist | • Standard follow up of hydronephrosis renal function1

• Frequency based on type of features

Development

| Monitor developmental progress educational needs.

Source: GeneReviews — "Schinzel-Giedion Syndrome"