Diagnostic Criteria

No consensus clinical diagnostic criteria for NFIX-related Malan syndrome (MALNS) have been published.

Suggestive Findings

MALNS should be suspected in individuals with at least five out of the following eight features [, , , ]:

• Prenatal overgrowth, often with a diagnosis of being large for gestational age

• Postnatal overgrowth (length/height and/or head circumference ≥2 standard deviations [SD] above mean for age and sex)

• Developmental delay/ intellectual disability

• Behavioral problems

• Distinctive facial features (See .)

• Advanced bone age and/or skeletal anomalies, such as scoliosis, pes planus, and pectus anomaly

• Slender body habitus

• Ocular findings, most commonly strabismus, refractive errors, and blue sclerae

Source: GeneReviews — "NFIX-Related Malan Syndrome"

Differential Diagnosis

Sotos syndrome

(SS), a syndromic overgrowth condition, is the primary differential diagnosis of NFIX-related Malan syndrome (MALNS). SS and MALNS are phenotypically similar and have overlapping clinical presentations but are distinguished by significant differences in the severity and frequency of several key features.

Source: GeneReviews — "NFIX-Related Malan Syndrome"

Management Guidelines

Suggested management and follow up recommendations for individuals with NFIX-related Malan syndrome (MALNS) have been published .

Evaluations Following Initial Diagnosis

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

Table 4.

NFIX-Related Malan Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Constitutional

| Measurement of weight, length/height, head circumference | To assess for macrocephaly postnatal overgrowth

Calculate BMI calorie intake. | In those age 2 years

Gastrointestinal/

Feeding

| Assess dietary intake variety of foods eaten. | • Consider eval for gastrostomy tube placement in persons w/dysphagia /or aspiration risk.

• If BMI is 2 SD below mean for age sex, reevaluate appropriateness of reported caloric intake.

Assess for signs/symptoms of constipation. |

Physical exam | • To screen for hepatomegaly, although most hepatomegaly described to date has not been assoc w/liver dysfunction

• Consider abdominal ultrasound if hepatomegaly is suspected by physical exam.

Neurologic

| Neurologic eval, incl for signs/symptoms of Chiari I malformation1 | Brain MRI should be considered for those w/concerning symptoms of Chiari I malformation or in those w/seizures.

Assess for signs/symptoms of seizures. | • Consider EEG if seizures are a concern.

Source: GeneReviews — "NFIX-Related Malan Syndrome"

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 — "NFIX-Related Malan 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. NFIX-Related Malan Syndrome: Recommended Surveillance

Source: GeneReviews — "NFIX-Related Malan Syndrome"