Neu-Laxova syndrome

Neu-Laxova syndrome (NLS) is an extremely rare, lethal autosomal recessive disorder characterized by severe intrauterine growth restriction, microcephaly, and multiple congenital anomalies. The condition was first described independently by Neu in 1971 and Laxova in 1972. It is caused by defects in the L-serine biosynthesis pathway, with pathogenic variants identified in the genes PHGDH (NLS type 1), PSAT1 (NLS type 2), and PSPH (NLS type 3). These genes encode enzymes essential for de novo serine synthesis, which is critical for normal fetal development. The syndrome affects multiple body systems and presents with a distinctive and recognizable phenotype. Key features include severe microcephaly with lissencephaly (smooth brain), marked ichthyosis (thickened, scaling skin), limb abnormalities including syndactyly and flexion contractures, severe edema (generalized subcutaneous swelling), exophthalmos (protruding eyes) with absent or hypoplastic eyelids, a flattened nose, micrognathia (small jaw), short neck, and hypoplasia of the external genitalia. Central nervous system malformations are prominent and include absent or hypoplastic corpus callosum, cerebellar hypoplasia, and neural tube defects. Skeletal abnormalities such as sloping forehead and limb shortening are also commonly observed. Neu-Laxova syndrome is almost invariably lethal, with most affected infants being stillborn or dying within hours to days after birth. There is currently no curative treatment, and management is limited to supportive and palliative care. Prenatal diagnosis is possible through ultrasound detection of characteristic anomalies and can be confirmed by molecular genetic testing. Genetic counseling is important for affected families, as carrier parents have a 25% recurrence risk with each pregnancy.

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