pigmentary retinopathy

Pigmentary Retinopathy with Congenital Sideroblastic Anemia

Clinical Characteristics
Ocular Features: 

The ocular phenotype has not been fully described, but several patients with a pigmentary retinopathy resembling retinitis pigmentosa have been reported.

Systemic Features: 

Patients present at a median age of two months with typically severe microcytic sideroblastic anemia. Median hemoglobin levels are 7.1 g/dl.  Lymphopenia and panhypogammaglobulinemia are usually present and many children have periodic febrile illnesses.  The number of CD19+ B cells is reduced.  Aminoaciduria, hypercalcinuria, and nephrocalcinosis have been observed.  Cardiomyopathy has been seen in several patients and may be responsible for the early demise.  Developmental delays may be severe with variable neurodegeneration features such as seizures, cerebellar symptoms, and sensorineural hearing loss.  Achievement of milestones is generally delayed.  Median survival is 4 years although one patient has lived to the age of 19 years.

Genetics

Homozygous mutations in TRNT1 (3p25.1) are responsible for this disorder.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Allogeneic bone marrow transplantation in one patient reversed the hematologic and immunologic anomalies although retinitis subsequently developed.

References
Article Title: 

Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD)

Chakraborty PK, Schmitz-Abe K, Kennedy EK, Mamady H, Naas T, Durie D, Campagna DR, Lau A, Sendamarai AK, Wiseman DH, May A, Jolles S, Connor P, Powell C, Heeney MM, Giardina PJ, Klaassen RJ, Kannengiesser C, Thuret I, Thompson AA, Marques L, Hughes S, Bonney DK, Bottomley SS, Wynn RF, Laxer RM, Minniti CP, Moppett J, Bordon V, Geraghty M, Joyce PB, Markianos K, Rudner AD, Holcik M, Fleming MD. Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood. 2014 Oct 30;124(18):2867-71.

PubMed ID: 
25193871

A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD)

Wiseman DH, May A, Jolles S, Connor P, Powell C, Heeney MM, Giardina PJ, Klaassen RJ, Chakraborty P, Geraghty MT, Major-Cook N, Kannengiesser C, Thuret I, Thompson AA, Marques L, Hughes S, Bonney DK, Bottomley SS, Fleming MD, Wynn RF. A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Blood. 2013 Jul 4;122(1):112-23.

PubMed ID: 
23553769

Cranial Dysinnervation Disorders with Strabismus and Arthrogryposis

Clinical Characteristics
Ocular Features: 

Strabismus and/or ophthalmoplegia are important features of a group of conditions known as cranial dysinnervation disorders.  Ptosis, Duane syndrome, V pattern exotropia and various degrees of ophthalmoplegia may be seen.  There may be considerable asymmetry in the manifestations in the two eyes.  Epicanthal folds, blepharophimosis, and hypermetropia are sometimes present.  Some patients have corneal leukomas, keratoglobus, high corneal astigmatism, and dysplastic optic disks. 

A pigmentary retinopathy and folds in the macula with an abnormal ERG has been reported.  Subnormal vision has been reported in some patients.

Systemic Features: 

Patients are often short in stature with pectus excavatum, spine stiffness, highly arched palate, and club feet.  Limited forearm rotation and wrist extension may be present.  The fingers appear long and often have contractures while the palmar and phalangeal creases may be absent.  Camptodactyly and clinodactyly are common.  Deep tendon reflexes are often hyporeactive and decreased muscle mass has been noted.  The muscles seem "firm" to palpation.  Restrictive lung disease has been reported.  Hearing loss is experienced by some individuals.

Genetics

Distal arthrogryposis type 5D is caused by homozygous or compound heterozygous mutations in the ECEL1 gene located at 2q36.  However, a similar phenotype (albeit with more severe ocular manifestations) results from heterozygous mutations in PIEZO2 (18p11).  Heterozygous mutations in the PIEZO2 gene have also been reported to cause distal arthrogryposis type 3 (Gordon syndrome [114300]) and Marden-Walker syndrome (248700) and all of these may be simply phenotypical variations of the same disorder.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

There is no treatment for this condition.  Patients with subnormal vision may benefit from low vision aids and selective surgery may be helpful in reducing the physical restrictions from physical deformities.

References
Article Title: 

Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5

McMillin MJ, Beck AE, Chong JX, Shively KM, Buckingham KJ, Gildersleeve HI, Aracena MI, Aylsworth AS, Bitoun P, Carey JC, Clericuzio CL, Crow YJ, Curry CJ, Devriendt K, Everman DB, Fryer A, Gibson K, Giovannucci Uzielli ML, Graham JM Jr, Hall JG, Hecht JT, Heidenreich RA, Hurst JA, Irani S, Krapels IP, Leroy JG, Mowat D, Plant GT, Robertson SP, Schorry EK, Scott RH, Seaver LH, Sherr E, Splitt M, Stewart H, Stumpel C, Temel SG, Weaver DD, Whiteford M, Williams MS, Tabor HK, Smith JD, Shendure J, Nickerson DA; University of Washington Center for Mendelian Genomics, Bamshad MJ. Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. Am J Hum Genet. 2014 May 1;94(5):734-44.

PubMed ID: 
24726473

Retinopathy with Neutropenia

Clinical Characteristics
Ocular Features: 

Pigmentary retinopathy was reported in a 25 year old female with moderately reduced visual acuity. Rare bone spicules pigment deposits were present in the periphery and macular edema was noted. Severely reduced scotopic and photopic responses were recorded.

Systemic Features: 

The single reported individual had congenital neutropenia and microcephaly. She had evident growth retardation and microcephaly at birth with subsequent recurrent upper respiratory infections and gingivitis. Speech and motor development were normal. Short stature was noted as well. The limbs were described as slender as in Cohen syndrome (216550) but no truncal obesity or joint hypermobility was present. The facial dysmorphism only vaguely resembled that found in Cohen syndrome (216550).

Genetics

This is a newly described condition whose unique identity remains to be established since only a single patient has been reported. This patient carried two heterozygous splicing mutations in the same VPS13B gene, the same gene in which more than 100 homozygous mutations have been found in individuals with Cohen syndrome (216550). Each parent carried a different splicing mutation in VPS13B.

Cohen syndrome (216550) however, has additional phenotypic features such as truncal obesity, intellectual disabilities, intermittent neutropenia, microcephaly, facial dysmorphism, myopia, and progressive chorioretinal dystrophy. Variable amounts of neutropenia were observed from age 5 years but the marrow was normocellular in appearance.

Isolated retinopathy with neutropenia may or may not be an autosomal recessive variant of Cohen syndrome (216550).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Nystagmus 6, Congenital, X-linked

Clinical Characteristics
Ocular Features: 

In several Chinese families, nystagmus was limited to males with onset in one case in the first 6 months.  Foveal dysplasia was present along with mottled fundus pigmentation.  Carrier females did not have nystagmus or changes in fundus pigmentation (except for one with mottling). Vision is in the range of 20/50-20/60.

Systemic Features: 

Skin and hair pigmentation was normal. No systemic disease was identified.

Genetics

Mutations in GPR143 (Xp22.2) have been identified in this form of nystagmus. The family pedigrees are consistent with X-linked recessive inheritance.

Two additional X-linked isolated nystagmus conditions are contained in this database: nystagmus 1 (310700), the result of mutations in FRMD7, and nystagmus 5 (300589) of unknown gene causation.

Several autosomal dominant forms have been linked to chromosomal regions 6p12 (NYS2; 164100), 7p11 (NYS3, 608345), 13q (NYS4, 193003), 1q31.3-q32.1, and NYS7 (614826).  Autosomal recessive inheritance has been proposed for several pedigrees but adequate documentation is lacking (see 257400).

Ocular albinism (OA1) (300500) can also result from mutations in GPR143.  However, there was no evidence of ocular or systemic hypopigmentation in the Chinese families.

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Aprataxin gene mutations in Tunisian families

Amouri R, Moreira MC, Zouari M, El Euch G, Barhoumi C, Kefi M, Belal S, Koenig M, Hentati F. Aprataxin gene mutations in Tunisian families. Neurology. 2004 Sep 14;63(5):928-9.

PubMed ID: 
15365154

Retinitis Pigmentosa 38

Clinical Characteristics
Ocular Features: 

This is a rare clinically heterogeneous condition in which both rods and cones functions are variably affected.  It is a progressive disorder with children often being aware of night vision difficulties during the latter half of the first decade of life.  Reduced vision is often present at this time as well and progressively deteriorates.  Visual fields are constricted to 20-30 degrees.  Rod responses may be nondetectable in the first decade.

Central vision is subnormal as early as childhood and progressively worsens with age.  Dyschromatopsia to some degree is often present early as well and some patients have a maculopathy with a bull’s eye pattern and thinning of the photoreceptor layer seen on OCT.  Attenuated retinal vessels, pale optic discs, and variable fundus pigmentary changes (including pigmentary mottling and bone spicules) have been seen.  The degree and course of the photoreceptor damage is variable leading some to propose that RP38 is primarily a cone-rod dystrophy.

Systemic Features: 

None

Genetics

This is an autosomal recessive disorder resulting from homozygous mutations in the MERTK gene (2q13).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported but young people especially could benefit from low vision aids and special education therapy.

References
Article Title: 

Retinal Cone Dystrophy 3B

Clinical Characteristics
Ocular Features: 

This is a degenerative disorder in which patients have a progressive deterioration of visual acuity and color vision.  Most patients have significant myopia.  Visual difficulties begin in early childhood with acuity of 20/100 or worse by the second decade of life.  Color vision deficits can be detected in the second decade but nyctalopia occurs later in young adults.  Photophobia is a prominent symptom.  The ERG shows reduced and delayed cone responses.  Rod responses to low intensity flashes are undetectable but increased stimulus intensity leads to an abrupt increase in amplitude, often exceeding the upper limits of normal.

The fundus appears normal in some patients but foveal or parafoveal atrophy, a macular bull’s eye, hyperfluorescence anomalies, and a generalized fine pigmentary retinopathy have been reported.  There may be some temporal pallor in the optic nerves.  Nystagmus and strabismus may be present.

Systemic Features: 

No systemic disease has been reported.

Genetics

This is an autosomal recessive disorder resulting from homozygous or compound heterozygous mutations in the KCNV2 gene (9p24.2).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment is available for this dystrophy.  Low vision aids and tinted lenses may be helpful.

References
Article Title: 

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 ) 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 occur in other conditions including a form of Bardet-Biedl Syndrome (209900), and Boucher-Neuhauser Syndrome (215470) also known as Chorioretinopathy, Ataxia, Hypogonadism Syndrome in this database.

Pedigree: 
Autosomal recessive
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

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

Retinitis Pigmentosa 25

Clinical Characteristics
Ocular Features: 

There is considerable clinical heterogeneity with a wide range in age of onset and progression.  Night blindness, sometimes with photophobia, has its onset in the second or third decade of life and central acuity can be impacted by age 30 years.  Other patients have no symptoms until the fifth decade.  Some patients lose the ability to perceive light by the sixth decade.  The visual fields are usually constricted although one patient had a central scotoma.  The ERG is usually nonrecordable but other patients may have a variable rod-cone pattern of attenuation.  The retinal vessels are also attenuated and some patients have mild optic atrophy.  The pigmentary retinopathy is also variable with sometimes central lesions and in other patients more peripheral.  One patient had posterior subcapsular cataracts.

Systemic Features: 

No systemic disease has been reported.

Genetics

This is an autosomal recessive form of retinitis pigmentosa resulting from homozygosity or compound heterozygosity in the EYS gene (6q12).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment has been reported.

References
Article Title: 

Knobloch Syndrome 3

Clinical Characteristics
Ocular Features: 

High myopia and marked nystagmus are cardinal ocular findings.  Night blindness leads to symptoms between 2 and 4 years of age.  Vision loss leads to complete blindness by age 15 to 18.  Visual acuity in young adults is often 20/400 to NLP.  Cataracts with subluxated lenses, glaucoma, and chorioretinal atrophy are often present.  Scattered pigment clumping, attenuation of the retinal vasculature, and prominent choroidal vessels can often be seen.  Marked optic atrophy is usually present.  Phthisis and band keratopathy may be seen in older individuals although no retinal detachments have been reported.  The vitreous is described as degenerated in several patients and a vitreal hemorrhage was seen in one patient.

Systemic Features: 

This variant was identified in a four-generation consanguineous Pakistani family in which detailed information was obtained in 5 members. A hairless, purplish-red patch is usually present in the occipital-parietal region during infancy but becomes smaller as children grow.  No encephalocele is present.  Hearing loss and heart defects have not been reported.  Intelligence is normal.

Genetics

This is an autosomal recessive condition resulting from a presumed homozygous mutation on chromosome 17 (17q11.2).

Other variants of Knobloch syndrome are Knobloch 1 (267750) caused by homozygous mutations in COL18A1 (21q22.3) and Knobloch 2 (608454) secondary to homozygous mutations in ADAMTS18 at 16q23.1.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Cataracts and dislocated lenses may be removed.

References
Article Title: 

Peroxisome Biogenesis Disorder 3B (Infantile Refsum Disease)

Clinical Characteristics
Ocular Features: 

This peroxisomal disorder presents in the first year of life with both systemic and ocular features.  Night blindness is the major ocular feature and at least some have optic atrophy similar to the adult form.  Nystagmus may be present.  Reduction or absence of rod responses on ERG can be used in young children to document the retinopathy. Blindness and deafness commonly occur in childhood.

Systemic Features: 

This disorder is classified as a peroxisomal biogenesis disorder (PBD) associated with the breakdown of phytanic acid.  Ataxia and features of motor neuron disease are evident early.  Hepatomegaly and jaundice may also be an early diagnostic feature as bile acid metabolism is defective.  Infant hypotonia is often seen.  Nonspecific facial dysmorphism has been reported as a feature. The teeth are abnormally large and often have yellowish discoloration.  Postural unsteadiness is evident when patients begin walking.  Diagnosis can be suspected from elevated serum phytanic and pipecolic acid (in 20% of patients) or by demonstration of decreased phytanic acid oxidation in cultured fibroblasts.  Other biochemical abnormalities such as hypocholesterolemia and elevated very long chain fatty acids and trihydroxycholestanoic acid are usually present.  Anosmia and mental retardation are nearly universal features.  Early mortality in infancy or childhood is common although some survive into the 2nd and 3rd decades.

Genetics

This is an autosomal recessive peroxisomal biogenesis disorder (PBD) resulting from mutations in a number of PEX genes (PEX1, PEX2, PEX3, PEX12, PEX26).  It shares many features with other PBDs including those formerly called Zellweger syndrome (214100), rhizomelic chondrodysplasia punctata (215100), and neonatal adrenoleukodystrophy (601539).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment is known.

References
Article Title: 

Pages

Subscribe to RSS - pigmentary retinopathy