Neu-Laxova syndrome 2

Neu-Laxova syndrome-2 (NLS2) is a rare autosomal recessive disorder characterized by severe congenital malformations leading to prenatal or early postnatal lethality.

Key Features:

• Abnormal craniofacial features [14]
• Microcephaly
• Intrauterine growth retardation
• Ichthyosis (skin abnormalities)
• Flexion deformities of the limbs

NLS2 is a rare and severe disorder, with affected individuals typically experiencing prenatal or early postnatal lethality. The exact cause of NLS2 is not well understood, but it is believed to be related to defects in enzymes involved in the L-Serine biosynthesis pathway [6].

References:

• [14] Description of Neu-Laxova syndrome-2 (NLS2)
• [6] Heterogeneous metabolic disorder caused by defects in enzymes of the L-Serine biosynthesis pathway.

Characteristics of Neu-Laxova Syndrome

Neu-Laxova syndrome (NLS) is a rare, multiple malformation syndrome characterized by severe intrauterine growth retardation (IUGR), severe microcephaly with a small head size, and distinct facial features. The signs and symptoms of NLS can vary in severity and may include:

• Facial Features: Babies with NLS often have characteristic facial features such as severe proptosis (bulging eyes) with ectropion (giving the impression of missing eyelids), hypertelorism (wide-set eyes), micrognathia (small lower jaw), flattened nose, and malformed ears [2].
• Skin Abnormalities: Ichthyosis, a condition characterized by dry, scaly skin, is often present in babies with NLS [4].
• Limb Deformities: Limb deformities, such as clubfoot or other skeletal abnormalities, may also be present [4].
• Brain and Muscle Abnormalities: Babies with NLS may have brain abnormalities, rigid muscles, and decreased fetal movements [1].

Other Possible Symptoms

In addition to the above symptoms, babies with NLS may also experience:

• Severe intrauterine growth restriction (IUGR)
• Microcephaly (small head size)
• Abnormal cortical gyration
• Abnormality of neuronal migration
• Abnormality of the cerebellar vermis

References

[1] Context result 1: Babies with NLS may also have extra fluid (edema) in their hands and feet, brain abnormalities, and rigid, stiff muscles.

[2] Context result 2: Facial features include severe proptosis with ectropion (giving the impression of missing eyelids), hypertelorism, micrognathia, flattened nose, and malformed ears.

[3] Context result 3: Typically, NLS involves characteristic facial features, decreased fetal movements and skin abnormalities.

[4] Context result 4: Neu-Laxova syndrome 1 is a rare autosomal recessive disorder characterized by severe intrauterine growth restriction, microcephaly, ichthyosis, limb deformities...

[5] Context result 5: Neu-Laxova syndrome (NLS) is a rare, multiple malformation syndrome characterized by severe intrauterine growth retardation (IUGR), severe microcephaly with a small head size, and distinct facial features.

[6] Context result 6: ORPHA:2671 Neu-Laxova syndrome · Abnormal cortical gyration HP:0002536 · Abnormality of neuronal migration HP:0002269 · Abnormality of the cerebellar vermis HP:

[7] Context result 7: by R Shaheen · 2014 · Cited by 113 — Neu-Laxova syndrome (NLS) is a rare autosomal-recessive disorder characterized by severe fetal growth restriction, microcephaly, a distinct facial appearance, ...

[8] Context result 8: Neu-Laxova syndrome is an autosomal recessive lethal multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, ...

Diagnostic Tests for Neu-Laxova Syndrome

Neu-Laxova syndrome (NLS) can be diagnosed prenatally or after birth through various diagnostic tests.

• Prenatal diagnosis: NLS can be suspected based on specialized testing, such as repeated fetal ultrasonography [3]. Fetal ultrasonography uses sound waves to create an image of the developing fetus. This test may reveal signs and symptoms associated with NLS, such as severe intrauterine growth retardation (IUGR), microcephaly, and facial dysmorphism.
• Genetic testing: Genetic testing can confirm the diagnosis of NLS. Prenatal genetic testing can be performed through chorionic villi sampling (CVS) or amniocentesis [4]. After birth, a genetic blood test can also confirm the diagnosis.
• Other diagnostic tests: Other diagnostic tests may include dermatology, genetics, neurology, and ophthalmology evaluations as part of the diagnostic team for NLS [1].

It's essential to note that the diagnosis of NLS is often suspected based on clinical signs and symptoms. However, genetic testing can confirm the presence of mutations in the PHGDH gene, which leads to a deficiency in serine production and causes NLS [8][9].

Treatment Options for Neu-Laxova Syndrome

Neu-Laxova syndrome (NLS) is a rare and severe genetic disorder that requires prompt and effective treatment to manage its symptoms and improve patient outcomes.

• Serine Supplementation: Research has shown that serine supplementation can be an attractive treatment option for NLS, particularly when administered during embryonic development. Studies have demonstrated that serine supplementation can help reduce the severity of NLS symptoms [4][8].
• Glycine Supplementation: In addition to serine, glycine supplementation has also been explored as a potential treatment for NLS. While more research is needed, preliminary studies suggest that glycine supplementation may be beneficial in managing NLS symptoms [2][6].
• Multidisciplinary Approach: Given the complexity of NLS, a multidisciplinary approach to care is essential. This includes collaboration between geneticists, pediatricians, and other specialists to provide comprehensive treatment and support for affected individuals and their families.

It's essential to note that each case of NLS is unique, and treatment plans should be tailored to individual needs. Patients with NLS must rely on a team of healthcare professionals to develop and implement an effective treatment plan [1].

References:

[1] Context 3 [2] Context 6 [4] Context 4 [8] Context 8

Differential Diagnosis of Neu-Laxova Syndrome 2 (NLS-2)

Neu-Laxova Syndrome 2 (NLS-2) is a rare and severe genetic disorder caused by mutations in the PSAT1 gene. The differential diagnosis of NLS-2 involves considering several other syndromes that present with similar clinical features.

Similar Syndromes:

• Cerebro-ocular-facial-skeletal (COFS) syndrome: This syndrome is characterized by intrauterine growth restriction, facial dysmorphism, and CNS malformations. It shares similarities with NLS-2 in terms of its severe growth delays before birth and distinctive craniofacial features [6].
• Walker-Warburg syndrome: This rare genetic disorder presents with CNS malformations, eye abnormalities, and muscle weakness. Like NLS-2, it can cause severe growth delays and intrauterine growth restriction [6].
• Pena-Shokeir phenotype: This syndrome is characterized by fetal akinesia or decreased in utero movement, leading to severe growth delays and distinctive craniofacial features. It shares similarities with NLS-2 in terms of its severe growth delays before birth and facial dysmorphism [7].

Other Considerations:

• Ichthyotic newborns: Neu-Laxova syndrome should be included in the differential diagnosis of ichthyotic newborns, as it can present with skin abnormalities such as ichthyosis [9].
• Central Nervous System (CNS) malformations: The underlying pathogenesis of NLS-2 involves CNS malformations, which should be considered in the differential diagnosis of reported cases [5].

References:

[1] - NLS caused by the mutation in the PSAT1 gene was classified as Neu Laxova 2 (NLS-2), with a phenotype very similar to 1. These genes are ...

[3] - Affected individuals have abnormal craniofacial features, microcephaly, intrauterine growth retardation, ichthyosis, flexion deformities, limb malformations, ...

[4] - by A Serrano Olave · 2022 · Cited by 7 — These manifestations include intrauterine growth restriction (IUGR), and facial dysmorphism with very characteristic features, such as proptosis, ichthyosis and ...

[6] - by H Aslan · 2002 · Cited by 26 — The differential diagnosis of the NLS should include cerebro-ocular-facial-skeletal (COFS) syndrome, Walker-Warburg syndrome, Pena-Shokeir ...

[7] - Aug 31, 2006 — Differential diagnosis of Neu-Laxova syndrome. Pena–Shokeir phenotype, A phenotype produced by foetal akinesia or decreased in utero movement ...

[8] - by D Özcan · Cited by 8 — Neu-Laxova syndrome is a rare, lethal, autosomal recessive disorder characterized by intrauterine growth retardation, central nervous system ...

[9] - by B Fakhir · 2020 · Cited by 2 — The positive diagnosis remains clinical postnatal. NLS should be included in the differential diagnosis of ichthyotic newborn.