Alternative titles; symbols
SNOMEDCT: 719944006; ORPHA: 3363; DO: 0111271;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19p13.2 | Oliver-McFarlane syndrome | 275400 | Autosomal recessive | 3 | PNPLA6 | 603197 |
A number sign (#) is used with this entry because of evidence that Oliver-McFarlane syndrome (OMCS) is caused by compound heterozygous mutation in the PNPLA6 (603197) gene on chromosome 19p13.
Laurence-Moon syndrome (LNMS; 245800) is an allelic disorder with overlapping features.
Oliver-McFarlane syndrome (OMCS) is a rare congenital disorder characterized by trichomegaly, severe chorioretinal atrophy, and multiple pituitary hormone deficiencies, including growth hormone (GH; 139250), gonadotropins (see 118860), and thyroid-stimulating hormone (TSH; see 118850). Thyroid and GH abnormalities may be present at birth and, if untreated, result in intellectual impairment and profound short stature. Congenital hypogonadism occurs in half of patients, and nearly all have documented hypogonadotropic hypogonadism during puberty, with subsequent reproductive dysfunction. Chorioretinal atrophy is typically noted in the first 5 years of life. Half of reported cases have spinocerebellar involvement, including ataxia, spastic paraplegia, and peripheral neuropathy (summary by Hufnagel et al., 2015).
Oliver and McFarlane (1965) described an isolated case of a male child with low-birth weight dwarfism, very long eyelashes and eyebrows, mental retardation, and pigmentary degeneration of the retina. The karyotype was normal and the parents were not consanguineous. Corby et al. (1971) reported a case of the full syndrome.
Delleman and Van Walbeek (1975) described a case in a 24-year-old man who had been under observation for 19 years. The retinal degeneration resembled choroideremia. Cryptorchidism, underdevelopment of the penis, frontal alopecia, and bulging of the occipital and frontal bones were noted. Partial trisomy of chromosome 13 was suggested by karyotyping.
Patton et al. (1986) reported a Caucasian male with typical features of Oliver-McFarlane syndrome. He presented at 2 years of age with failure to thrive. At that time, he was noted to have long eyelashes (20 mm) with bushy eyebrows and sparse scalp hair. These features had been present at birth. He had a small penis and his testes were not palpable. Examination of his fundi showed extensive peripheral and central choroidoretinal degeneration with pallor of the optic discs. He attended a school for the visually handicapped and had an IQ of 89. At age 10 years he developed obesity and gynecomastia. At age 18, he remained hypogonadal with no secondary characteristics. Endocrine studies showed evidence of hypothyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. When examined at age 37, he gave a 2-year history of progressive gait ataxia, generalized clumsiness, and titubation of the head. Brain scan showed cerebellar atrophy and an empty sella. Nerve conduction studies showed small or absent sensory action potentials with preserved motor nerve conduction velocities, suggesting an axonal peripheral neuropathy.
Sampson et al. (1989) presented a 25-year follow-up of a patient. The father and mother were aged 37 and 28 years, respectively, at the time of the patient's birth. At the age of 2 years, she showed horizontal nystagmus and bilateral choroidoretinal pigmentary degeneration. Ring heterochromia of the iris and trichomegaly were also noted. Alopecia became evident by age 3 and was almost complete by the early teens. Scalp biopsy showed a perifollicular lymphocyte infiltrate which was similar to that seen in alopecia areata. Distal muscle weakness and wasting, affecting particularly the lower limbs, progressed slowly during her first decade. An axonal peripheral neuropathy was found in this patient and in the adult reported by Patton et al. (1986). When the patient was seen at age 15 because of delayed puberty, she was found to have growth hormone deficiency and hypogonadotropic hypogonadism. Treatment with growth hormone resulted in a growth spurt with a final adult height of 153 cm. Zaun et al. (1984) reported a case.
Kondoh et al. (2003) stated that 2 female and 5 male patients with this disorder had been reported. They described 2 unrelated boys with trichomegaly and mental retardation, but without pigmentary retinal degeneration. One of them also lacked growth retardation.
Haimi and Gershoni-Baruch (2005) described a brother and sister, born of first-cousin Arab parents, who had retinitis pigmentosa, growth failure with mildly delayed cognitive function, long eyelashes, and sparse hair. Haimi and Gershoni-Baruch (2005) concluded that these sibs confirmed the existence of this autosomal recessive condition.
Sonmez et al. (2008) described a 13-year-old boy with Oliver-McFarlane syndrome who had prominent early pituitary dysfunction. During the neonatal period he had episodes of recurrent hypoglycemia and was noted to have micropenis and bilateral undescended testes, and thyroid and growth hormone supplementation was initiated. Gross motor development was delayed, and he did not walk independently until 4 years of age; however, his gait was wide-based and unsteady, and he was found to have sensory axonal neuropathy with normal motor nerve findings. Four years later, his sensory nerve action potentials were completely absent, but motor nerve function remained normal. Within a year his walking deteriorated, and he reverted to commando crawling. In addition, at 5 years of age, he had difficulty seeing in low light, and ophthalmologic examination revealed bilateral decreased vision and dramatic choroidal and retinal atrophy associated with retinal pigmentation. At 13 years of age, he could crawl short distances but was otherwise wheelchair dependent, had a moderate degree of learning difficulties, and remained incontinent. He was in the 3rd centile for height and 50th centile for weight, and had long eyelashes, bushy eyebrows, and frontal bossing. He also had hypogonadotropic hypogonadism, and testosterone injections had been commenced to induce puberty. Sonmez et al. (2008) stated that of 12 previously reported cases of Oliver-McFarlane syndrome, the only consistent features in every case were trichomegaly, chorioretinopathy, and prenatal and postnatal growth restrictions. Regarding the progressive deterioration in motor function in their patient, which had been attributed to his severe peripheral neuropathy, the authors noted that peripheral neuropathy had been recognized in 6 earlier cases, and 2 patients also showed evidence of progressive cerebellar ataxia.
The transmission pattern of Oliver-McFarlane syndrome in the family reported by Haimi and Gershoni-Baruch (2005) was consistent with autosomal recessive inheritance.
In 6 patients from 5 families with a clinical diagnosis of Oliver-McFarlane syndrome, Hufnagel et al. (2015) identified compound heterozygous mutations in the PNPLA6 gene (see, e.g., 603197.0013-603197.0016). The mutations were found in 3 families by exome-sequencing and in the other 2 families by Sanger sequencing. Familial carrier testing, which was possible in 3 families, showed segregation of the mutation with the phenotype.
Corby, D. G., Lowe, R. S., Jr., Haskins, R. C., Hebertson, L. M. Trichomegaly, pigmentary degeneration of the retina, and growth retardation. Am. J. Dis. Child. 121: 344-345, 1971. [PubMed: 5550742] [Full Text: https://doi.org/10.1001/archpedi.1971.02100150118018]
Delleman, J. W., Van Walbeek, K. The syndrome of trichomegaly, tapetoretinal degeneration and growth disturbances. Ophthalmologica 171: 313-315, 1975. [PubMed: 1165905] [Full Text: https://doi.org/10.1159/000307536]
Haimi, M., Gershoni-Baruch, R. Autosomal recessive Oliver-McFarlane syndrome: retinitis pigmentosa, short stature (GH deficiency), trichomegaly, and hair anomalies or CPD syndrome (chorioretinopathy-pituitary dysfunction). Am. J. Med. Genet. 138A: 268-271, 2005. [PubMed: 16152639] [Full Text: https://doi.org/10.1002/ajmg.a.30953]
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]
Kondoh, T., Amamoto, N., Hirota, T., Kinoshita, E., Moriuchi, H., Matsumoto, T., Shimono, M., Kawakami, A., Shirahata, A. Very long eyelashes, long eyebrows, sparse hair, and mental retardation in two unrelated boys: an atypical form of Oliver-McFarlane syndrome without retinal degeneration, or a new clinical entity? (Letter) Am. J. Med. Genet. 120A: 437-438, 2003. [PubMed: 12838570] [Full Text: https://doi.org/10.1002/ajmg.a.20049]
Oliver, G. L., McFarlane, D. C. Congenital trichomegaly with associated pigmentary degeneration of the retina, dwarfism and mental retardation. Arch. Ophthal. 74: 169-171, 1965. [PubMed: 14318490] [Full Text: https://doi.org/10.1001/archopht.1965.00970040171008]
Patton, M. A., Harding, A. E., Baraitser, M. Congenital trichomegaly, pigmentary retinal degeneration, and short stature. Am. J. Ophthal. 101: 490-491, 1986. [PubMed: 3963113] [Full Text: https://doi.org/10.1016/0002-9394(86)90656-2]
Sampson, J. R., Tolmie, J. L., Cant, J. S. Oliver-McFarlane syndrome: a 25-year follow-up. Am. J. Med. Genet. 34: 199-201, 1989. [PubMed: 2816997] [Full Text: https://doi.org/10.1002/ajmg.1320340213]
Sonmez, S., Forsyth, R. J., Matthews, D. S. F., Clarke, M., Splitt, M. Oliver-McFarlane syndrome (chorioretinopathy-pituitary dysfunction) with prominent early pituitary dysfunction: differentiation from choroideremia-hypopituitarism. Clin. Dysmorph. 17: 265-267, 2008. [PubMed: 18978655] [Full Text: https://doi.org/10.1097/MCD.0b013e328306a374]
Zaun, H., Stenger, D., Zabransky, S., Zankl, M. Das Syndrom der langen Wimpern ('Trichomegaliesyndrom' Oliver McFarlane). Hautarzt 35: 162-165, 1984. [PubMed: 6715173]