XLMR with Cerebellar Hypoplasia and Distinctive Facial Appearance: OPHN1 Gene Deletion/Duplication

Condition Description

Mutations in the OPHN1 gene (Xq12) are associated withX-linked mental retardation with subtle facial dysmorphism and cerebellaranomalies, including hypoplasia of the vermis, expansion of the cisterna magna,and retrocerebellar cysts. Phenotypic features can include neonatal hypotoniawith motor delay but no obvious ataxia, marked strabismus, early-onset complexpartial seizures, and moderate to severe intellectual disability. Other affected individualswith OPHN1 mutations are reported tohave moderate to severe intellectual disability associated with enlargement of thelateral ventricles and cerebellar hypoplasia, seizures, ataxia, strabismus, andhypogenitalism with cryptorchidism, hypoplastic scrotum, and microphallus.

Facial features associated with OPHN1 mutations include mild facialdysmorphism with long face, prominent forehead, deep-set eyes, markedinfraorbital creases, strabismus, short or upturned philtrum, and large ears. Obligatefemale carriers have been reported to show subtle facial changes and/or reducedcerebellar size in some cases.

In one study, four different novelmutations were identified in the OPHN1gene: two mutations were found in a group of 17 unrelated males with mental retardationand known cerebellar anomalies (12%) and two mutations were found in a group of196 unrelated males with X-linked intellectual disability without previous brainimaging studies (1%). Retrospective imaging studies, when possible, detectedcerebellar hypoplasia in the latter patients.

Both point mutations and deletionshave been reported in the OPHN1 gene.

Click here for the OMIM summary on this condition.

Genes (1)

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This test is indicated for:

  • Confirmation of a clinical diagnosis of XLMR with cerebellar hypoplasia and distinctive facial appearance in individuals who have tested negative for sequence analysis
  • Carrier testing in adult females with a family history of XLMR with cerebellar hypoplasia and distinctive facial appearance who have tested negative for sequence analysis


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.

  • Sequencing analysis of the OPHN1 gene is available (YR) and is required before deletion/duplication analysis.
  • A CGH array-based test for deletion/duplication analysis of 64 different X-linked intellectual disability genes is available (OL).
  • Prenatal testing is available to adult females who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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