Clinical Guidance

Males and females can present similarly with Simpson-Golabi-Behmel syndrome type 1 (SGBS1). However, there is skewing of males to females in a 9:1 ratio. Individuals of both sexes present with overgrowth, characteristic facial features, skeletal abnormalities, and genitourinary dysfunction. Males often present with cryptorchidism. Females are less likely to present with significant manifestations of SGBS1, potentially due to skewed X-chromosome inactivation. There have not been extensive studies of sex differences in SGBS1 due to the small number of females reported to date and mildly affected or unaffected female carriers who do not present until they have an affected son. Affected Males SGBS1 is characterized by pre- and postnatal overgrowth, distinctive facies, and variable visceral, skeletal, and neurodevelopmental abnormalities. To date, more than 180 individuals have been identified with a pathogenic variant in GPC3 . The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Simpson-Golabi-Behmel Syndrome Type 1: Frequency of Select Features

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

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.

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