Clinical Guidance

Although no specific genotype-phenotype correlations have been conclusively identified, biallelic predicted loss-of-function variants (e.g., frameshift, nonsense) appear to have a greater degree of severity of ID and increased frequency of seizures when compared with biallelic protein-altering variants (e.g., missense, inframe indels).

Source: GeneReviews — "KPTN-Related Disorder"

Diagnostic Criteria

Suggestive Findings

KPTN-related disorder should be considered in probands with the following clinical, laboratory, and neuroimaging findings and family history.

Clinical findings

Source: GeneReviews — "KPTN-Related Disorder"

Differential Diagnosis

Table 3. Disorders Associated with Macrocephaly and Intellectual Disability/ Developmental Delay in the Differential Diagnosis of KPTN-Related Disorder

Management Guidelines

No clinical practice guidelines for KPTN-related disorder have been published.

Evaluations Following Initial Diagnosis

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

Table 4.

KPTN-Related Disorder: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Development

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

• To incl assessment for balance problems oral apraxia

• Eval for early intervention/ special education

Neurobehavioral/

Psychiatric

| Neuropsychiatric eval | For persons age 12 months: screening for neurobehavioral/psychiatric manifestations incl anxiety, stereotypies, impaired social interaction, hyperactivity

Neurologic

| Assessment of head circumference |

Neurologic eval | Low threshold for EEG if seizures are a concern.

Immunology

| Assessment for recurrent infections incl otitis media respiratory tract infections |

Hearing

| Audiology eval | Assessment for recurrent otitis conductive hearing impairment

Ophthalmologic

| Eval by ophthalmologist | Assessment for strabismus, nystagmus, amblyopia

Endocrine

| • Assessment for hypoglycemia in neonatal period, in infancy, w/intercurrent illness

• Assessment for hypo- hyperthyroidism hyperprolactinemia

|

Skeletal manifestations

| Assessment for joint hypermobility, scoliosis, chest wall deformity |

Source: GeneReviews — "KPTN-Related Disorder"

Therapies Under Investigation

Current studies of the efficacy of mTOR inhibitors are under way in KPTN-related disorder mouse models. 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.

Source: GeneReviews — "KPTN-Related Disorder"

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. KPTN-Related Disorder: Recommended Surveillance

Source: GeneReviews — "KPTN-Related Disorder"