Neu-Laxova Syndrome Health Article

Definition

Neu-Laxova syndrome is a rare disorder characterized by the onset of severe growth delay during pregnancy, multiple birth defects, and abnormal physical development of the brain. Affected infants typically die shortly after delivery or are stillborn.

Description

In 1971, Dr. Neu published the first report of a family that included three children with a unique pattern of multiple birth defects. Each child had an unusually small head (microcephaly) and abnormalities of their arms, legs, skin, and external genitalia. The two affected daughters were each stillborn, while the affected son only lived for seven weeks. In 1972, Dr. Laxova described a different family whose children had birth defects similar to those first described by Dr. Neu. The parents in this second family were first cousins to one another. Taken together, these two families were considered evidence of a previously unrecognized genetic syndrome. The disorder was named Neu-Laxova syndrome in honor of these two physicians.

Neu-Laxova syndrome (NLS) has since become known as a rare, lethal inherited condition characterized by a specific pattern of facial, brain, and limb abnormalities. Other associated abnormalities often include dry, scaly skin, generalized swelling of body tissues (edema), and extremely slow growth.

Genetic profile

Neu-Laxova syndrome is inherited as an autosomal recessive condition. Males and females are equally likely to be affected. It has been reported in a variety of ethnic groups. Proof of autosomal recessive inheritance includes the birth of more than one affected child to normal parents, and the observed incidence of infants with NLS among the children of two blood relatives. Consanguinity, or the mating of two biologically related individuals, increases the possibility of having a child with a genetic disorder. Since any two relatives will share a portion of their genes in common, they are more likely to each be a carrier of the same autosomal recessive gene.

In order to be affected with NLS, an individual must inherit two copies of the NLS gene, or one copy from each carrier parent. A carrier has one NLS gene and one normal gene; as such, a NLS carrier appears completely normal. However, two carriers face a risk of 25%, or a one in four chance, of having a child with NLS. Conversely, they also have a 75% chance of having an unaffected child. These risks apply to each of their pregnancies together.

Infants with NLS have also been born to non-consanguineous, or unrelated, couples. Anytime a child with NLS is born, the parents must be obligate, or mandatory, carriers of one NLS gene. As such, they face an increased risk in future pregnancies together of having another affected child.

The gene for NLS has not yet been identified. Thus, it is not possible to perform direct genetic testing to determine carrier status, confirm a clinical diagnosis, or provide accurate prenatal diagnosis.

Demographics

Adequate data are not available to provide a specific statistic regarding the frequency of NLS. The condition is very rare. According to a 1995 publication, only 40 cases of Neu-Laxova syndrome had been reported up to that point in the medical literature.

Signs and symptoms

Stillborn or newborn infants with NLS have a characteristic pattern of internal and external abnormalities. Not all affected infants will have all of the features listed below, and some anomalies are slightly more common than others.

Infants with Neu-Laxova syndrome often have unusual facial features. Their heads are very small, and their foreheads appear to slant backwards. The distance between the eyes is wider than normal (hypertelorism), and the eyes are prominent or bulging. Cataracts may be present. The eyelids are typically absent. The bridge of the nose is wide and slightly flattened. The ears are abnormally shaped. The lower jaw appears recessed as compared to the upper jaw (retrognathia), and the mouth itself is usually open with abnormally thick lips. Cleft lip may be present, with or without cleft palate.

The external features of the head and face are a reflection of severe physical abnormalities of the brain. It is not unusual for an infant with NLS to have an underdeveloped cerebellum or even lissencephaly, a more serious malformation characterized by a smooth brain surface. Normal development of the brain includes an intricate pattern of grooves, or gyri, on its outer surface. A lack of these grooves leads to profound mental retardation among survivors and an increased frequency of medical complications, such as seizures. Other reported brain malformations include agenesis of the corpus callosum and Dandy-Walker malformation.

A variety of limb abnormalities have also been described in NLS. Affected individuals often have shortened arms and legs that are held out from the body in an unusual, fixed position. This positioning is often referred to as flexion contractures. The fingers and toes may appear underdeveloped (hypoplastic) and/or fused together (syndactyly). The heels of the feet are often rounded (rocker-bottom feet), and the neck is short.

Other abnormalities more common to NLS include markedly limited physical growth. This typically begins during pregnancy and, as such, is referred to as intrauterine growth restriction (IUGR). Edema, or an excessive amount of fluid in the tissues of the body, is a hallmark of NLS. The edema may either be generalized and very severe throughout the body or limited only to the face or scalp. The skin is often extremely dry and scaly, a medical condition called ichthyosis. The lungs are often hypoplastic (underdeveloped), even when delivery occurs at term. The external genitalia are often abnormal, but this is more obvious in males than in females since males typically have a small, underdeveloped penis.

Finally, in addition to IUGR during pregnancy, an excessive volume of amniotic fluid (polyhydramnios) often develops. This is due to a combination of abnormal fluid production and impaired fetal swallowing from the associated nervous system abnormalities. The placenta is also usually abnormal in appearance and function.