Clinical Guidance

There are no known clinically relevant genotype-phenotype correlations for SGBS1 to date.

Source: GeneReviews — "Simpson-Golabi-Behmel Syndrome Type 1"

Penetrance

All males reported with a GPC3 pathogenic variant have clinical findings of SGBS1. Penetrance in heterozygous females is unknown, but unaffected or mildly affected females have been reported .

Source: GeneReviews — "Simpson-Golabi-Behmel Syndrome Type 1"

Diagnostic Criteria

For the purposes of this GeneReview, the terms "male" and "female" are narrowly defined as the individual's biological sex at birth as it determines clinical care . Consensus clinical diagnostic criteria for Simpson-Golabi-Behmel syndrome type 1 (SGBS1) have not been established.

Suggestive Findings

SGBS1 should be suspected in probands with the following clinical findings and family history.

Clinical findings

• Linear somatic overgrowth

• Macrocephaly

• Characteristic facial features

Source: GeneReviews — "Simpson-Golabi-Behmel Syndrome Type 1"

Differential Diagnosis

Table 3.

Disorders to Consider in the Differential Diagnosis of Simpson-Golabi-Behmel Syndrome Type 1

Gene(s) | Disorder | MOI | Clinical Features of Disorder

Overlapping w/SGBS1 | Distinguishing from SGBS1

See footnote 1. | Beckwith-Wiedemann syndrome (BWS) | See footnote 1. | • Macrosomia

• Macroglossia

• Ear anomalies

• Diastasis recti

• Hypoglycemia

• Genitourinary malformations

• incidence of tumors

| • Appreciably different facial features (midface flattening in BWS; broader forehead in SGBS1)

Source: GeneReviews — "Simpson-Golabi-Behmel Syndrome Type 1"

Management Guidelines

No clinical practice guidelines for Simpson-Golabi-Behmel syndrome type 1 (SGBS1) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with SGBS1, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Simpson-Golabi-Behmel Syndrome Type 1: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Oropharynx

| Assess for macroglossia orofacial clefting. | Referral to craniofacial team incl feeding specialists

Eyes | Ophthalmologic exam |

Ears/Hearing

| Audiologic eval |

Cardiac

| Consider chest radiograph, EKG, echocardiogram. | To evaluate for structural heart defects conduction abnormalities

Respiratory

| Assess for upper-airway sufficiency signs/symptoms of sleep apnea; consider formal sleep study. | Particularly in those w/hypotonia macroglossia

Renal

| Exam for hypospadias undescended testes in males; renal ultrasound to assess for renal anomalies | Referral to urologist as needed

Abdomen/Pelvis

| Abdominal/pelvic ultrasound to initiate tumor screening | Further studies (e.g., MRI) may be indicated if findings are suspicious for a tumor.

Measurement of serum AFP | As a baseline screen for hepatoblastoma

Musculoskeletal

| Clinical eval for scoliosis | Particula...

Source: GeneReviews — "Simpson-Golabi-Behmel Syndrome Type 1"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Simpson-Golabi-Behmel Syndrome Type 1"

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 6. Simpson-Golabi-Behmel Syndrome Type 1: Recommended Surveillance for Males

Source: GeneReviews — "Simpson-Golabi-Behmel Syndrome Type 1"