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Writer's pictureJonathan Colaco

Neu-Lexova Syndrome

Just a quick preface: I am NOT a licensed physician. I am a high school student who enjoys researching interesting medical phenomena. I just enjoy writing about medicine and science!


Neu-Laxova syndrome also known as NLS is an extremely rare genetic disorder inherited as an autosomal recessive trait. NLS is caused by mutations in one of three genes PHGDH, PSAT1, or PSPH. The mutations that cause NLS result in a severe L-serine deficiency. L-serine is the precursor of other amino acids, phospholipids, and sphingolipids. Specifically, L-serine plays an extensive role in protein synthesis and intracellular metabolism. In embryonic development, L-Serine is heavily involved in the de novo creation of purine nucleotides (Adenine and Guanine). This foundational L-serine deficiency leads to a halt in cell proliferation and growth which is consistent with the characteristic intrauterine growth retardation. NLS is part of a group of diseases known as serine biosynthesis defects and is characterized by intrauterine growth retardation or severe growth delays before birth, low birth weight and length, and distinct abnormalities of the craniofacial region. These

craniofacial abnormalities include microcephaly or smallness of the head, sloping of the forehead, widely spaced eyes, underdeveloped jaw, malformed ears, and ocular malformations. Together these along with other distinct abnormalities create a very distinctive appearance making postnatal diagnosis very easy. Abnormal accumulations of fluid in the tissues throughout the body, permanent flexion, and immobilization of multiple joints, other limb malformations, along with various brain, skin, genital, kidney, and heart abnormalities are also common with NLS. Signs of NLS are almost always present before birth. These potential signs of NLS pre-birth include excessive fluid in the amniotic sac, abnormally small placenta, short umbilical cord, and reduced fetal movement. Due to the underdeveloped nature of the newborn NLS often causes total underdevelopment of all body systems including having only one kidney, underdeveloped gyri or folds of the brain, underdeveloped heart chambers, and skin webbing. It is important to note that several of the known NLS cases were caused by parents that were closely related by blood. Incestual relationships mean that both parents are more likely to carry the same mutated gene for the same disease trait so therefore there is an increased risk that their children may inherit the two genes necessary for the development of NLS or other conditions. In addition, NLS has also been known to be caused via a de novo mutation. Diagnosis of NLS may be suggested prenatally with the use of repeated fetal ultrasonography or genetic testing. Treatment of the condition is solely based on treating specific symptoms. Only about 60 cases of Neu-Laxova syndrome have been reported with an estimated incidence of less than 1 in 1 million births. The prognosis, however, is poor as most newborns are stillborn or die soon after birth. However, L-serine supplementation is a potential treatment if the condition can be identified early enough prenatally.


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