Lujan syndrome (formerly Lujan–Fryns syndrome)

Lujan syndrome (formerly Lujan–Fryns syndrome) is a genetic disorder that can affect neurodevelopment, mental health, and multiple organ systems. It is classically an X-linked disorder and predominantly affects males; affected females are uncommon. Most affected males inherit the pathogenic variant from an unaffected carrier mother, although de novo pathogenic variants and maternal mosaicism (the pathogenic variant is present in some maternal cells but not others) can occur. The phenotype may resemble Marfan syndrome and classic homocystinuria, particularly in its tall, slender habitus, long limbs, and long fingers, but these conditions are genetically distinct. Lujan syndrome is particularly associated with intellectual and developmental impairment, characteristic facial features, and hypernasal speech, whereas classic homocystinuria may be distinguished by ectopia lentis, thromboembolic disease, and biochemical abnormalities including elevated homocysteine. A distinctive presentation of Lujan syndrome may include the combination of tall, slender habitus, macrocephaly, a long narrow face, long fingers with hyperextensibility, and hypernasal speech.

It can present with psychiatric features such as hyperactivity, emotional lability, shyness, aggression, autistic behaviours, and psychosis. Psychiatric manifestations may become apparent during adolescence or adulthood, and psychotic disorders, including schizophrenia, have been reported.

From a morphologic lens perspective, other features include (but are not limited to):

• Macrocephaly

• Prominent forehead

• Prominent nasal bridge

• Downslanted palpebral fissures

• Ptosis

• Short philtrum

• Micrognathia

• Low-set ears

• Long fingers

Other characteristic features include mild-to-moderate intellectual disability, developmental delay, hypotonia, speech and language difficulties, including hypernasal speech, and seizures in some individuals. Abnormalities of the corpus callosum may also occur. A high narrow palate and maxillary hypoplasia may also be present.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

• Musculoskeletal: tall, slender or marfanoid habitus, long hyperextensible fingers and toes, joint hyperextensibility, pectus excavatum, and other skeletal abnormalities may occur.

• Cardiovascular: congenital cardiac abnormalities have been reported in individual cases, but they are not a defining or consistently frequent feature of Lujan syndrome.

Early diagnosis is important to identify potentially treatable medical contributors to psychiatric, developmental, and cognitive presentations, recognize associated neurologic and musculoskeletal complications, guide appropriate developmental, educational, and behavioral support, and enable timely recognition and treatment of psychosis and other psychiatric comorbidities.