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Developmental delay-facial dysmorphism syndrome due to MED13L deficiency
Disease definition
A rare, genetic syndromic intellectual disability characterized by developmental delay, mild to severe intellectual disability, facial features (bulbous nasal tip, and macroglossia, macrostomia, or open mouth appearance) and a wide spectrum of other nonspecific variable clinical features.
ORPHA:369891
Classification level: Disorder- Synonym(s):
- MED13L-related intellectual disability syndrome
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal dominant
- Age of onset: Infancy, Neonatal
- ICD-10: Q87.8
- OMIM: 616789
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
Summary
Epidemiology
To date, more than 70 cases have been reported.
Clinical description
Patients have a variable degree of intellectual disability, global developmental delay (notably with severe speech and language impairment), muscular hypotonia, and facial features (including broad forehead, bitemporal narrowing, upslanting palpebral fissures, low-set ears, flat nasal bridge, bulbous nose, thin vermillion border and open mouth with tongue protrusion). Highly variable additional features include cardiac defects (persistent foramen ovale, ventricular septal defects or tetralogy of Fallot), cerebellar ataxia, seizures, growth difficulties, microcephaly, ventriculomegaly or myelination defects.
Etiology
The disorder is sporadic caused by either a sequence variation in the mediator complex subunit 13-like gene (MED13L), an intragenic microdeletion within the gene, or by a larger microdeletion encompassing the entire gene. Rare intragenic microduplications within MED13L are also reported.
Diagnostic methods
The syndrome could be suspected on the association of developmental delay, speech impairment, motor delay, and facial features (notably, an open mouth with a protruding tongue, a thin vermillion border, upslanting palpebral fissures and a bulbous nasal tip). Molecular genetic testing approaches include array-comparative genomic hybridization for microdeletion identification, and sequencing of the entire MED13L coding region for sequence variants (gene panel, exome sequencing).
Differential diagnosis
Some patients share some clinical features observed in Kleefstra syndome, Mowat-Wilson syndrome, Kabuki syndrome and 1p36 microdeletion.
Antenatal diagnosis
Pathogenic variations are de novo. However, very rare cases of parental mosaicism are described and prenatal genetic testing may be possible in such families with a proband. No specific prenatal signs are reported.
Genetic counseling
Most cases arise de novo and thus the sibling recurrence risk is low. The disorder is autosomal dominant with 50% risk of transmission from affect individuals to their offspring; however, transmission of the condition has never been reported.
Management and treatment
Management is mainly supportive and symptomatic. Affected patients should benefit from speech therapy. Development, walking evolution, hearing and vision should be monitored closely.
Prognosis
The prognosis and function consequences are variable and dependent on the associated anomalies and intellectual disability.
A summary on this disease is available in Deutsch (2019) Italiano (2019) Español (2020) Français (2020) Nederlands (2020)
Detailed information
Guidelines
- Clinical practice guidelines
- Français (2022) - PNDS
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