ORPHA: 2671, 583602; DO: 0080075;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 9q21.2 | Neu-Laxova syndrome 2 | 616038 | Autosomal recessive | 3 | PSAT1 | 610936 |
A number sign (#) is used with this entry because of evidence that Neu-Laxova syndrome-2 (NLS2) is caused by homozygous or compound heterozygous mutation in the PSAT1 gene (610936) on chromosome 9q21.
Neu-Laxova syndrome-2 (NLS2) is a rare autosomal recessive disorder characterized by a recognizable pattern of severe congenital malformations leading to prenatal or early postnatal lethality. Affected individuals have abnormal craniofacial features, microcephaly, intrauterine growth retardation, ichthyosis, flexion deformities, limb malformations, and edema of the hands and feet. Some patients have malformations of the central nervous system, such as abnormal gyration (summary by Acuna-Hidalgo et al., 2014).
For a discussion of genetic heterogeneity of Neu-Laxova syndrome, see NLS1 (256520).
Acuna-Hidalgo et al. (2014) reported 9 patients from 6 unrelated families with Neu-Laxova syndrome-2. Four of the families were consanguineous. Clinical details of the 6 probands were provided. The most common features included craniofacial dysmorphism with microcephaly, sloping forehead, low-set or malformed ears, flat or abnormal nose, micrognathia, and an abnormal round, gaping mouth. More variable features included hypertelorism, proptosis, and absent or abnormal eyelids; 1 fetus had cleft palate. Two affected patients were liveborn, but died within the first 2 weeks of life; the rest were stillborn.
The transmission pattern of NLS2 in the families reported by Acuna-Hidalgo et al. (2014) was consistent with autosomal recessive inheritance.
In affected fetuses and newborns from 6 unrelated families with Neu-Laxova syndrome-2, Acuna-Hidalgo et al. (2014) identified homozygous or compound heterozygous mutations in the PSAT1 gene (610936.0003-610936.0005). The mutations, which were found by homozygosity mapping combined with detailed exome sequencing, were confirmed by Sanger sequencing. The mutations segregated with the disorder in all families with available material; functional studies were not performed. Acuna-Hidalgo et al. (2014) noted that some features of the phenotype overlapped with, but were more severe than, those reported in patients with PSAT deficiency, suggesting that the prenatal lethality of NLS2 represents the more severe end of a phenotypic spectrum. The findings emphasized the critical importance of serine availability in early embryonic and fetal development.
Acuna-Hidalgo, R., Schanze, D., Kariminejad, A., Nordgren, A., Kariminejad, M. H., Conner, P., Grigelioniene, G., Nilsson, D., Nordenskjold, M., Wedell, A., Freyer, C., Wredenberg, A., and 18 others. Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. Am. J. Hum. Genet. 95: 285-293, 2014. [PubMed: 25152457] [Full Text: https://doi.org/10.1016/j.ajhg.2014.07.012]