Clinical Guidance

Genotype-phenotype correlations have not been possible to date given the rarity of the condition and limited number of pathogenic variants described.

Source: GeneReviews — "FREM1 Autosomal Recessive Disorders"

Genetic testing for FREM1 is available. Testing is considered confirmatory for diagnosis.

Table 3.

MOTA Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Ocular

| Ophthalmologic eval | For coloboma /or keratopathy

ENT | Eval for bifid nose/ notched ala nasi | Referral to plastic surgeon as needed

Gastrointestinal

| Eval for anal anomalies, omphalocele, /or umbilical hernia | Referral to surgeon if present

Kidneys

| Kidney imaging, kidney functional analysis | For kidney malformation function

Genetic counseling

| By genetics professionals1 | To obtain a pedigree inform affected persons their families re nature, MOI, implications of MOTA syndrome to facilitate medical personal decision making

MOI = mode of inheritance; MOTA = Manitoba oculotrichoanal

1. Clinical geneticist, certified genetic counselor, certified genetic nurse, genetics advanced practice provider (nurse practitioner or physician assistant)

Table 4.

BNAR Syndrome: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "FREM1 Autosomal Recessive Disorders"

Family/Community

| Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning). | At each visit

Source: GeneReviews — "FREM1 Autosomal Recessive Disorders"

Phenotype severity distribution: 1 always present feature, 1 very common feature, 11 common features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).