Penetrance

All individuals with SRS have deficient spermine synthase enzyme activity. However, as its prevalence in the general population has not been determined, penetrance of deficient spermine synthase activity as SRS cannot be estimated.

Source: GeneReviews — "Snyder-Robinson Syndrome"

Diagnostic Criteria

Formal diagnostic criteria have not been established for Snyder-Robinson syndrome (SRS).

Suggestive Findings

SRS should be suspected in males with the following clinical findings and family history.

Clinical findings

• Developmental delay. Generalized psychomotor delay that begins in infancy typically affecting motor and speech development

• Hypotonia due to poor muscular development

• Ambulation abnormalities ranging from unsteady gait to inability to walk

• Speech abnormalities. Nasal, dysarthric, coarse, or absent speech

• Intellectual disability (ID). Typically in the moderate-to-severe range, but mild ID as well as profound ID have been described

• Asthenic body build and diminished body bulk

Source: GeneReviews — "Snyder-Robinson Syndrome"

Differential Diagnosis

X-linked intellectual disability (ID) syndromes with osteoporosis. Distinguishing between various forms of syndromic ID by clinical findings alone is often difficult because of overlapping clinical features, and diagnosis generally requires identification of the molecular cause. Nonetheless, Snyder-Robinson syndrome (SRS) can be distinguished from many forms of syndromic X-linked ID by the combination of hypotonia, facial dysmorphism, asthenic body build, and both early-onset osteoporosis and kyphoscoliosis. While kyphoscoliosis is visible, osteoporosis is not, although the presence of fractures is suggestive of it. Because osteoporosis is rare in X-linked ID, it can be utilized as a distinguishing feature and should certainly be considered in a male with fractures. X-linked ID syndromes with overlapping findings of SRS and osteoporosis are summarized in . Table 3. X-Linked Intellectual Disability Syndromes with Overlapping Findings of Snyder-Robinson Syndrome and Osteoporosis

Management Guidelines

Management guidelines are provided in several languages by the Snyder-Robinson Foundation. The following recommendations are based on management guidelines and 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 SRS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Snyder-Robinson Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Development

| Developmental assessment | • To incl motor, adaptive, cognitive, speech-language eval

• Eval for early intervention/ special education

Neurologic

| Neurologic eval | • Assessment for hypotonia

• To incl brain MRI to assess abnormal calcification /or brain abnormalities

• Consider EEG if seizures are a concern.

Constitutional

| Weight, length/height, head circumference | Assess for evidence of short stature, macrocephaly.

Musculoskeletal

| Bone density assessment by DXA scan | To determine degree of osteoporosis need for calcium supplements or bisphosphonates1

Clinical eval for kyphoscoliosis, joint contractures, pectus deformities | Consider radiographic scoliosis survey based on clinical suspicion referral for orthopedic surgery as appropriate.

Cleft palate

| Clinical eval incl feeding assessment |

Genitourinary

| • Assessment for hypospadias cryptorchism

• Renal ultrasound

Source: GeneReviews — "Snyder-Robinson 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 6. Snyder-Robinson Syndrome: Recommended Surveillance

Source: GeneReviews — "Snyder-Robinson Syndrome"