Penetrance

MFDM is highly penetrant but variably expressive. Features may be subclinical in some affected individuals, as in the case of two non-mosaic, intellectually normal mothers – each with two affected children – in whom the only reported clinical findings were unilateral zygomatic cleft and facial asymmetry and mild facial asymmetry and a preauricular tag .

Source: GeneReviews — "Mandibulofacial Dysostosis with Microcephaly"

Diagnostic Criteria

Suggestive Findings

Mandibulofacial dysostosis with microcephaly (MFDM) should be suspected in individuals with mandibulofacial dysostosis (a developmental disorder of the first and second branchial arches characterized by malar and maxillary hypoplasia) in the context of one or more additional features, including:

Source: GeneReviews — "Mandibulofacial Dysostosis with Microcephaly"

Differential Diagnosis

Mandibulofacial Dysostosis

Table 3.

Genes of Interest in the Differential Diagnosis of Mandibulofacial Dysostosis with Microcephaly

Gene(s) | DiffDx Disorder | MOI | Clinical Characteristics of DiffDx Disorder Overlapping w/MFDM | Distinguishing Features

CHD71 | CHARGE syndrome(See CHD7 Disorder.) | AD | Microcephaly, ear anomalies, choanal atresia, TEF, CHD | Ocular coloboma Mondini malformation are present in CHARGE but not in MFDM.

DHODH

| Miller acrofacial dysostosis(OMIM 263750) | AR | MFD w/postaxial limb defects ± other extracranial malformations | OFC intelligence are typically normal in Miller acrofacial dysostosis.

POLR1C

POLR1D

TCOF1

| Treacher Collins syndrome (TCS) | ADAR | • MFD (may resemble MFD in MFDM)

Source: GeneReviews — "Mandibulofacial Dysostosis with Microcephaly"

Management Guidelines

Evaluations Following Initial Diagnosis

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

Table 4.

Recommended Evaluations Following Initial Diagnosis in Individuals with Mandibulofacial Dysostosis with Microcephaly

System/Concern | Evaluation | Comment

MFD | • Airway assessment for evidence of upper-airway obstruction w/or w/o choanal atresia

• Exam for midline cleft palate referral to multidisciplinary cleft palate team as required

| Important in newborns w/disorder

DD/ID

| Developmental assessment | Incl adaptive, cognitive, speech-language evals

Hearing loss

| Audiologic eval | Assess for hearing loss.

EA/TEF

| Urgent eval in newborns, esp in those w/history of polyhydramnios, unexplained respiratory distress, /or failed nasogastric tube placement |

Cardiac anomaly

| Echocardiogram cardiologist eval |

Renal anomaly

| Renal ultrasound |

Skeletal

anomaly | Radiograph to assess for scoliosis, rib or thumb malformation as clinically indicated |

Short stature

| Assess w/growth charts. | Height growth curves for MFDM are published.1

Genetic

counseling | By genetics professionals2 | To inform affected persons families re nature, MOI, implications of MFDM to facilitate medical personal decision making

Family support

resources | Assess need for:

Source: GeneReviews — "Mandibulofacial Dysostosis with Microcephaly"

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 — "Mandibulofacial Dysostosis with Microcephaly"

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with MFDM

Source: GeneReviews — "Mandibulofacial Dysostosis with Microcephaly"