Clinical Guidance

No clinically relevant genotype-phenotype correlations have been identified.

Source: GeneReviews — "UNC80 Deficiency"

Diagnostic Criteria

Suggestive Findings

UNC80 deficiency should be suspected in probands with the following clinical features:

• Developmental delay with severe motor delays and absent speech (less than five words)

• Neonatal hypotonia

• Severe intellectual disability

• Strabismus

• Dyskinesia of the limbs

• Postnatal growth deficiency with postnatal microcephaly in some individuals

• Sleeplessness and irritability

• Constipation

• Seizures in some individuals

Establishing the Diagnosis

The diagnosis of UNC80 deficiency is established in a proband with and biallelic pathogenic (or likely pathogenic) variants in UNC80 identified by molecular genetic testing . Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that bot...

Source: GeneReviews — "UNC80 Deficiency"

Differential Diagnosis

Disorders to consider in the differential diagnosis are listed in .

Table 3.

Selected Disorders in the Differential Diagnosis of UNC80 Deficiency

Gene/ Genetic Mechanism | Disorder | MOI | Distinguishing Clinical Features

Abnormal parent-specific imprinting w/in PWCR | Prader-Willi syndrome | See footnote 1. | Neonatal hypotonia poor weight gain followed by obesity, polyphagia, thin vermilion of upper lip w/downturned corners of mouth, genitourinary anomalies, delayed acquisition of speech mobility

Deficient expression or function of maternally inherited UBE3A allele | Angelman syndrome | See footnote 1. | Bursts of laughter, macrostomia, tongue protrusion, prognathism, widely spaced teeth, mild cortical atrophy

MECP2

| Classic Rett syndrome (See MECP2 Disorders.) | XL1 | Lack of dysmorphic facia...

Source: GeneReviews — "UNC80 Deficiency"

Management Guidelines

No clinical practice guidelines for UNC80 deficiency have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with UNC80 deficiency, the evaluations and referrals summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 4. UNC80 Deficiency: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "UNC80 Deficiency"

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 — "UNC80 Deficiency"

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.

UNC80 Deficiency: Recommended Surveillance

System/Concern | Evaluation | Frequency

Development

| Monitor developmental progress educational needs. | Annually

Neurobehavioral/

Psychiatric

| Behavioral assessment for hypersensitivity /or self-injurious behavior

Neurologic

| Assessment to identify manage seizures

Ophthalmologic involvement

| Ophthalmology exam for ocular manifestations

Growth/Feeding

| • Measurement of growth parameters

• Eval of nutritional status safety of oral intake

| At each visit

Gastrointestinal

| Assessment for constipation

Musculoskeletal

| • Orthopedist eval of contractures back exam for scoliosis

• Physical medicine, OT/PT assessment of mobility, self-help skills

| Annually

OT = occupational therapy; PT = physical therapy

Source: GeneReviews — "UNC80 Deficiency"