SNOMEDCT: 232059000, 5619004; ICD10CM: Q87.84; ORPHA: 2377; DO: 1930;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19p13.2 | ?Laurence-Moon syndrome | 245800 | Autosomal recessive | 3 | PNPLA6 | 603197 |
A number sign (#) is used with this entry because of evidence that Laurence-Moon syndrome (LNMS) is caused by compound heterozygous mutation in the PNPLA6 gene (603197) on chromosome 19p13. One such family has been reported.
Oliver-McFarlane syndrome (OMCS; 275400) is an allelic disorder with overlapping features.
Laurence-Moon syndrome (LNMS) has a clinical presentation similar to that of Oliver-McFarlane syndrome (275400), including chorioretinopathy and pituitary dysfunction, but with childhood onset of ataxia, peripheral neuropathy, and spastic paraplegia and without trichomegaly. Historically, Laurence-Moon syndrome has been associated with Bardet-Biedl syndrome (see BBS, 209900) (summary by Hufnagel et al., 2015).
The features in the 4 sibs reported by Laurence and Moon (1866) and later by Hutchinson (1882, 1900) were mental retardation, pigmentary retinopathy, hypogenitalism, and spastic paraplegia. Solis-Cohen and Weiss (1925) considered the disorder identical to Bardet and Biedl syndrome; they used the designation Laurence-Biedl syndrome. The existence of a separate entity was suggested by Bowen et al. (1965) and others.
Chalvon-Demersay et al. (1993) reported a family with Laurence-Moon syndrome in which 5 members had retinopathy, mental retardation, and first metacarpal hypoplasia with proximal placement of the thumb. In addition to growth retardation and hypogonadism, all 5 had had spastic paraplegia since the age of 5 to 6 years. Four of the patients (2 girls, 2 boys) had low basal plasma levels of follicle- stimulating hormone (FSH; see 136530) and luteinizing hormone (LH; see 152780). Hufnagel et al. (2015) examined 2 affected members of this family, a 42-year-old female and a 41-year-old male, and found abnormal pituitary hormone concentrations, including low gonadotropins. Brain MRI demonstrated small anterior pituitary size. Fundus examination showed diffuse choroidal and retinal pigment atrophy with peripapillary sparing. Hand x-rays demonstrated contractures consistent with spastic paraplegia. Both patients had prominent chins. The woman had normal eyelash length and mild frontal scalp alopecia; the male had long eyelashes, bushy eyebrows, and prominent frontal bone, suggestive of Oliver-McFarlane syndrome.
In a 22-year prospective cohort study of 46 patients from 26 Newfoundland families with BBS, Moore et al. (2005) found no apparent correlation of clinical or dysmorphic features with genotype. They reported that of 2 patients clinically diagnosed as having Laurence-Moon syndrome, one was from a consanguineous pedigree with linkage to the BBS5 gene, and the other was a compound heterozygote for mutations in the MKKS gene (604896.0007 and 604896.0008). Moore et al. (2005) concluded that the features in this population did not support the notion that BBS and Laurence-Moon syndrome are distinct. The patient with mutations in the MKKS gene (NF-B5) had previously been reported by Katsanis et al. (2000) as having BBS6, thus illustrating the difficulty in distinguishing these 2 disorders.
Hufnagel et al. (2015) considered the Laurence-Moon and Bardet-Biedl syndromes to be distinct, given the marked choroidal atrophy, hypopituitarism with short stature, early neurologic involvement, and the absence of polydactyly and renal disease in Laurence-Moon syndrome. They also noted that the retinal degeneration is distinct, with Laurence-Moon and Oliver-McFarlane syndromes resembling choroideremia, and BBS resembling cone-rod dystrophy or retinitis pigmentosa with choroidal sparing.
The transmission pattern of Laurence-Moon syndrome in the family reported by Chalvon-Demersay et al. (1993) was consistent with autosomal recessive inheritance.
Farag and Teebi (1988) concluded that both the Bardet-Biedl and the Laurence-Moon syndromes are increased in the Arab population of Kuwait.
In affected members of a family with a clinical diagnosis of Laurence-Moon syndrome, originally reported by Chalvon-Demersay et al. (1993), Hufnagel et al. (2015) identified compound heterozygous mutations in the PNPLA6 gene (603197.0013; 603197.0017). The mutations, which were found by exome sequencing, segregated with the disorder in the family. The mutations were not found in over 300 ethnically matched controls or in the 1000 Genomes Project or Exome Variant Server databases.
Roth (1947) described 4 brothers of Czechoslovakian extraction, with unrelated parents, who had infantile external genitalia, hypogonadotropic hypogonadism, gynecomastia, and retinal degeneration. One was notably obese.
Bowen, P., Ferguson-Smith, M. A., Mosier, D., Lee, C. S. N., Butler, H. G. The Laurence-Moon syndrome. Association with hypogonadotrophic hypogonadism and sex-chromosome aneuploidy. Arch. Intern. Med. 116: 598-604, 1965. [PubMed: 5835363] [Full Text: https://doi.org/10.1001/archinte.116.4.598]
Chalvon-Demersay, A., Tardieu, M., Crosnier, H., Benichou, J. J., Pienkowski, C., Rochiccioli, P., Labrune, B. Syndrome de Laurence-Moon (Bardet-Biedl) avec deficit en hormone de croissance. Arch. Franc. Pediat. 50: 859-862, 1993. [PubMed: 8053762]
Farag, T. I., Teebi, A. S. Bardet-Biedl and Laurence-Moon syndromes in a mixed Arab population. Clin. Genet. 33: 78-82, 1988. [PubMed: 3359670] [Full Text: https://doi.org/10.1111/j.1399-0004.1988.tb03414.x]
Hufnagel, R. B., Arno, G., Hein, N. D., Hersheson, J., Prasad, M., Anderson, Y., Krueger, L. A., Gregory, L. C., Stoetzel, C., Jaworek, T. J., Hull, S., Li, A., and 20 others. Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes. J. Med. Genet. 52: 85-94, 2015. [PubMed: 25480986] [Full Text: https://doi.org/10.1136/jmedgenet-2014-102856]
Hutchinson, J. On retinitis pigmentosa and allied affections, as illustrating the laws of heredity. Ophthal. Rev. 1: 2-7 and 26-30, 1882.
Hutchinson, J. Slowly progressive paraplegia and disease of the choroids with defective intellect and arrested sexual development. Arch. Surg. 11: 118-122, 1900.
Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome. Nature Genet. 26: 67-70, 2000. [PubMed: 10973251] [Full Text: https://doi.org/10.1038/79201]
Laurence, J. Z., Moon, R. C. Four cases of retinitis pigmentosa occurring in the same family and accompanied by general imperfection of development. Ophthal. Rev. 2: 32-41, 1866.
Moore, S. J., Green, J. S., Fan, Y., Bhogal, A. K., Dicks, E., Fernandez, B. A., Stefanelli, M., Murphy, C., Cramer, B. C., Dean, J. C. S., Beales, P. L., Katsanis, N., Bassett, A. S., Davidson, W. S, Parfrey, P. S. Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study. Am. J. Med. Genet. 132A: 352-360, 2005. [PubMed: 15637713] [Full Text: https://doi.org/10.1002/ajmg.a.30406]
Roth, A. A. Familial eunuchoidism: the Laurence-Moon-Biedl syndrome. J. Urol. 57: 427-442, 1947. [PubMed: 20286155] [Full Text: https://doi.org/10.1016/S0022-5347(17)69652-6]
Solis-Cohen, S., Weiss, E. Dystrophia adiposogenitalis with atypical retinitis pigmentosa and mental deficiency: the Laurence-Biedl syndrome. Am. J. Med. Sci. 169: 489-505, 1925.