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X-linked intellectual disability with marfanoid habitus
The Lujan-Fryns syndrome or X-linked mental retardation (XLMR) with marfanoid habitus syndrome is a syndromic X-linked form of intellectual disability, associated with tall, marfanoid stature, distinct facial dysmorphism and behavioral problems.
ORPHA:776Classification level: Disorder
The syndrome affects predominantly males. The prevalence in the general population is not known.
Patients present tall stature, long hyper-extensible fingers and toes, short halluces and long second toes. Patients have mild to moderate intellectual disability. Craniofacial features include long forehead, long narrow face, maxillary hypoplasia, small mandible, long nose with high and narrow nasal bridge, short and deep philtrum, thin upper lip and highly arched palate. The marfanoid stature becomes evident after puberty. In adulthood, patients are tall but height is in the normal range. A hypernasal voice and generalized hypotonia are often present. Secondary sexual development and testicular size are normal. Behavioral features include emotional instability, hyperactivity and shyness. Psychiatric disorders such as psychotic disturbances with hallucinatory visions and sounds, and schizophrenia can be present.
The Lujan-Fryns syndrome is a developmental disorder of genetic origin. In the original Lujan family, a novel missense mutation in the mediator complex subunit 12, MED12 gene (Xq13) was found as the cause of Lujan-Fryns syndrome. Defects in this gene also cause FG syndrome (see this term). In some cases, mutations in the UPF3B gene (Xq25-q26) and in the ZDHHC9 gene (Xq26.1) have been reported in XLMR with marfanoid habitus.
Diagnosis is based on the clinical manifestations and can be confirmed by the presence of the missense mutation in the MED12 gene. However, the frequency of the presence of a mutation in patients with the clinical diagnosis of Lujan-Fryns syndrome is not known.
Differential diagnosis includes the fragile X syndrome (molecular analysis of the FMR-1 gene), Marfan syndrome (cardiac and ophthalmologic examination) (see these terms), and homocystinuria (biochemical analysis). Lujan-Fryns syndrome should be considered in the differential diagnosis of schizophrenia.
There is currently no specific prenatal test for this condition. However, prenatal diagnosis for at-risk pregnancies first requires identification of the mutations in the family. Molecular analysis of the MED12 gene in chorionic villus samples is possible.
Genetic counseling, based on the X-linked mode of inheritance, should be offered to patients with a prior identified MED12 gene mutation. In sporadic cases, a recurrence risk of 25% for the following pregnancy should be considered.
Management and treatment
There is no specific treatment for this condition. Patients require specialized education and psychological follow-up. Psychiatric disorders (psychosis) should be diagnosed as early as possible.
Data on life expectancy are not available as most reports describe patients in adolescence and young adulthood. Special attention should be given to comorbidity and behavioral problems.