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Trichomegaly-retina pigmentary degeneration-dwarfism syndrome(OMCS)

MedGen UID:
338532
Concept ID:
C1848745
Disease or Syndrome
Synonyms: Eyelashes long mental retardation; Eyelashes, long with mental retardation; Oliver-McFarlane syndrome; Trichomegaly retina pigmentary degeneration dwarfism; Trichomegaly with mental retardation, dwarfism and pigmentary degeneration of retina
SNOMED CT: Trichomegaly with retina pigmentary degeneration and dwarfism syndrome (719944006); Oliver McFarlane syndrome (719944006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): PNPLA6 (19p13.2)
 
Monarch Initiative: MONDO:0010152
OMIM®: 275400
Orphanet: ORPHA3363

Disease characteristics

Excerpted from the GeneReview: PNPLA6 Disorders
PNPLA6 disorders span a phenotypic continuum characterized by variable combinations of cerebellar ataxia; upper motor neuron involvement manifesting as spasticity and/or brisk reflexes; chorioretinal dystrophy associated with variable degrees of reduced visual function; and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). The hypogonadotropic hypogonadism occurs either in isolation or as part of anterior hypopituitarism (growth hormone, thyroid hormone, or gonadotropin deficiencies). Common but less frequent features are peripheral neuropathy (usually of axonal type manifesting as reduced distal reflexes, diminished vibratory sensation, and/or distal muscle wasting); hair anomalies (long eyelashes, bushy eyebrows, or scalp alopecia); short stature; and impaired cognitive functioning (learning disabilities in children; deficits in attention, visuospatial abilities, and recall in adults). Some of these features can occur in distinct clusters on the phenotypic continuum: Boucher-Neuhäuser syndrome (cerebellar ataxia, chorioretinal dystrophy, and hypogonadotropic hypogonadism); Gordon Holmes syndrome (cerebellar ataxia, hypogonadotropic hypogonadism, and – to a variable degree – brisk reflexes); Oliver-McFarlane syndrome (trichomegaly, chorioretinal dystrophy, short stature, intellectual disability, and hypopituitarism); Laurence-Moon syndrome; and spastic paraplegia type 39 (SPG39) (upper motor neuron involvement, peripheral neuropathy, and sometimes reduced cognitive functioning and/or cerebellar ataxia). [from GeneReviews]
Authors:
Matthis Synofzik  |  Robert B Hufnagel  |  Stephan Züchner   view full author information

Additional description

From OMIM
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).  http://www.omim.org/entry/275400

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Hypoplasia of penis
MedGen UID:
78603
Concept ID:
C0266435
Congenital Abnormality
Severe short stature
MedGen UID:
3931
Concept ID:
C0013336
Disease or Syndrome
A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Long eyebrows
MedGen UID:
481761
Concept ID:
C3280131
Finding
Increased length of the hairs of the eyebrows.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Long eyelashes
MedGen UID:
342955
Concept ID:
C1853738
Finding
Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective).
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.
Delayed puberty
MedGen UID:
46203
Concept ID:
C0034012
Pathologic Function
Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.
Hypogonadotropic hypogonadism
MedGen UID:
82883
Concept ID:
C0271623
Disease or Syndrome
Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones
Decreased response to growth hormone stimulation test
MedGen UID:
1784655
Concept ID:
C5539399
Finding
Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Retinal degeneration
MedGen UID:
48432
Concept ID:
C0035304
Finding
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells.
Central heterochromia
MedGen UID:
867209
Concept ID:
C4021567
Sign or Symptom
The presence of distinct colors in the central (pupillary) zone of the iris than in the mid-peripheral (ciliary) zone.
Pigmentary retinopathy
MedGen UID:
1643295
Concept ID:
C4551715
Disease or Syndrome
An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVTrichomegaly-retina pigmentary degeneration-dwarfism syndrome
Follow this link to review classifications for Trichomegaly-retina pigmentary degeneration-dwarfism syndrome in Orphanet.

Recent clinical studies

Etiology

Hutchison DM, Duffens A, Yale K, Park A, Cardenas K, Mesinkovska NA
J Eur Acad Dermatol Venereol 2022 Apr;36(4):536-546. Epub 2021 Dec 31 doi: 10.1111/jdv.17877. PMID: 34919300
Lisbjerg K, Andersen MKG, Bertelsen M, Brost AG, Buchvald FF, Jensen RB, Bisgaard AM, Rosenberg T, Tümer Z, Kessel L
Ophthalmic Genet 2021 Aug;42(4):464-473. Epub 2021 Apr 5 doi: 10.1080/13816810.2021.1904419. PMID: 33818269
Teive HAG, Camargo CHF, Sato MT, Shiokawa N, Boguszewski CL, Raskin S, Buck C, Seminara SB, Munhoz RP
Cerebellum 2018 Jun;17(3):380-385. doi: 10.1007/s12311-017-0909-y. PMID: 29248984Free PMC Article
Chang TS, McFarlane DC, Oliver G, Willis NR
Can J Ophthalmol 1993 Jun;28(4):191-3. PMID: 8343920
Sampson JR, Tolmie JL, Cant JS
Am J Med Genet 1989 Oct;34(2):199-201. doi: 10.1002/ajmg.1320340213. PMID: 2816997

Diagnosis

Liu J, Hufnagel RB
Ophthalmic Genet 2023 Dec;44(6):530-538. Epub 2023 Nov 20 doi: 10.1080/13816810.2023.2254830. PMID: 37732399Free PMC Article
Kumari S, Bagraniya V, Kumar V
Ophthalmol Retina 2023 Nov;7(11):1009. Epub 2023 Jun 13 doi: 10.1016/j.oret.2023.05.009. PMID: 37318400
Lisbjerg K, Andersen MKG, Bertelsen M, Brost AG, Buchvald FF, Jensen RB, Bisgaard AM, Rosenberg T, Tümer Z, Kessel L
Ophthalmic Genet 2021 Aug;42(4):464-473. Epub 2021 Apr 5 doi: 10.1080/13816810.2021.1904419. PMID: 33818269
Makuloluwa AK, Dodeja R, Georgiou M, Gonzalez-Martin J, Hagan R, Madhusudhan S, Michaelides M
Ophthalmic Genet 2020 Oct;41(5):451-456. Epub 2020 Jun 25 doi: 10.1080/13816810.2020.1783689. PMID: 32586184
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
J Med Genet 2015 Feb;52(2):85-94. Epub 2014 Dec 5 doi: 10.1136/jmedgenet-2014-102856. PMID: 25480986Free PMC Article

Therapy

Makuloluwa AK, Dodeja R, Georgiou M, Gonzalez-Martin J, Hagan R, Madhusudhan S, Michaelides M
Ophthalmic Genet 2020 Oct;41(5):451-456. Epub 2020 Jun 25 doi: 10.1080/13816810.2020.1783689. PMID: 32586184
Shaker AG, Fleming R, Jamieson ME, Yates RW, Coutts JR
Hum Reprod 1994 Nov;9(11):1997-8. doi: 10.1093/oxfordjournals.humrep.a138381. PMID: 7868663

Prognosis

Liu J, Hufnagel RB
Ophthalmic Genet 2023 Dec;44(6):530-538. Epub 2023 Nov 20 doi: 10.1080/13816810.2023.2254830. PMID: 37732399Free PMC Article
Lisbjerg K, Andersen MKG, Bertelsen M, Brost AG, Buchvald FF, Jensen RB, Bisgaard AM, Rosenberg T, Tümer Z, Kessel L
Ophthalmic Genet 2021 Aug;42(4):464-473. Epub 2021 Apr 5 doi: 10.1080/13816810.2021.1904419. PMID: 33818269
Makuloluwa AK, Dodeja R, Georgiou M, Gonzalez-Martin J, Hagan R, Madhusudhan S, Michaelides M
Ophthalmic Genet 2020 Oct;41(5):451-456. Epub 2020 Jun 25 doi: 10.1080/13816810.2020.1783689. PMID: 32586184
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
J Med Genet 2015 Feb;52(2):85-94. Epub 2014 Dec 5 doi: 10.1136/jmedgenet-2014-102856. PMID: 25480986Free PMC Article
Chang TS, McFarlane DC, Oliver G, Willis NR
Can J Ophthalmol 1993 Jun;28(4):191-3. PMID: 8343920

Clinical prediction guides

Liu F, Ji Y, Li G, Xu C, Sun Y
Gene 2020 Nov 30;761:145027. Epub 2020 Aug 3 doi: 10.1016/j.gene.2020.145027. PMID: 32758583
Makuloluwa AK, Dodeja R, Georgiou M, Gonzalez-Martin J, Hagan R, Madhusudhan S, Michaelides M
Ophthalmic Genet 2020 Oct;41(5):451-456. Epub 2020 Jun 25 doi: 10.1080/13816810.2020.1783689. PMID: 32586184

Recent systematic reviews

Hutchison DM, Duffens A, Yale K, Park A, Cardenas K, Mesinkovska NA
J Eur Acad Dermatol Venereol 2022 Apr;36(4):536-546. Epub 2021 Dec 31 doi: 10.1111/jdv.17877. PMID: 34919300

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