Trichomegaly Plus Syndrome

Clinical Characteristics

Ocular Features:

Eyelashes are described as ‘long’, and the eyebrows are bushy. The majority of individuals have poor vision secondary to severe receptor dysfunction. Night blindness and severe photophobia are features in some cases. Both retinal and choroidal atrophy have been diagnosed in the first 5 years of life and most patients have a progressive and extensive pigmentary retinopathy.

Systemic Features:

Scalp alopecia and sparse body hair is common in spite of the trichomegaly of the eyebrows and eyelashes. Frontal bossing has been noted in some patients. Pituitary dysfunction is suggested by low growth hormone levels, features of hypogonadotropic hypogonadism, and possibly hypothyroidism.

Some deficit of cognitive function is usually present and a few patients have been described as mentally retarded. There is evidence of progressive neurological damage both centrally and peripherally. Developmental milestones are often achieved late and some individuals have been observed to regress during the first decade of life. The peripheral neuropathy includes both sensory and motor components. Sensory nerve action potentials may be lost in the first decade while early motor functions may regress during the same period. Several patients have had evidence of progressive cerebellar ataxia.

Genetics

Compund heterozygous mutations in PNPLA6 (19p13.2), coding for neuropathy target esterase, have been found in several patients presumed to have this condition. Autosomal recessive inheritance has been proposed on the basis of a single family in which an affected brother and sister were born to first cousin parents.

The relationship of this disorder to that found in two cousins, offspring of consanguineous matings, described as ‘cone-rod congenital amaurosis associated with congenital hypertrichosis: an autosomal recessive condition’ (204110 [1] ) is unknown. They were described as having visual impairment from birth and profound photophobia. Fundus changes were minimal with a bull’s eye pattern of pigment changes in the macula described as indicative of a rod-cone congenital amaurosis. ERG responses were unrecordable. These individuals apparently did not have other somatic, psychomotor or neurologic deficits.

Mutations in PNPLA6 [2] occur in other conditions including a form of Bardet-Biedl Syndrome [3] (209900 [4]), and Boucher-Neuhauser Syndrome [5] (215470 [6]) also known as Chorioretinopathy, Ataxia, Hypogonadism Syndrome [5] in this database.

Treatment

Treatment Options:

No treatment is available for this condition although growth hormone and testosterone supplementation have been reported to have the appropriate selective effects.

References

Article Title:

Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes [7]

Hufnagel RB, Arno G, Hein ND, Hersheson J, Prasad M, Anderson Y, Krueger LA, Gregory LC, Stoetzel C, Jaworek TJ, Hull S, Li A, Plagnol V, Willen CM, Morgan TM, Prows CA, Hegde RS, Riazuddin S, Grabowski GA, Richardson RJ, Dieterich K, Huang T, Revesz T, Martinez-Barbera JP, Sisk RA, Jefferies C, Houlden H, Dattani MT, Fink JK, Dollfus H, Moore AT, Ahmed ZM. Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes. J Med Genet. 2015 Feb;52(2):85-94.

PubMed ID:

25480986

Oliver-McFarlane syndrome (chorioretinopathy-pituitary dysfunction) with prominent early pituitary dysfunction: differentiation from choroideremia-hypopituitarism [8]

Sonmez S, Forsyth RJ, Matthews DS, Clarke M, Splitt M. Oliver-McFarlane syndrome (chorioretinopathy-pituitary dysfunction) with prominent early pituitary dysfunction: differentiation from choroideremia-hypopituitarism. Clin Dysmorphol. 2008 Oct;17(4):265-7.

PubMed ID:

18978655

Autosomal recessive Oliver-McFarlane syndrome: retinitis pigmentosa, short stature (GH deficiency), trichomegaly, and hair anomalies or CPD syndrome (chorioretinopathy-pituitary dysfunction) [9]

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 A. 2005 Oct 15;138A(3):268-71.

PubMed ID:

16155639

Cone-rod congenital amaurosis associated with congenital hypertrichosis: an autosomal recessive condition. [10]

Jalili IK. Cone-rod congenital amaurosis associated with congenital hypertrichosis: an autosomal recessive condition. J Med Genet. 1989 Aug;26(8):504-10.

PubMed ID:

2769722