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Fraser syndrome 1(FRASRS1)

MedGen UID:
1639061
Concept ID:
C4551480
Disease or Syndrome
Synonyms: Cryptophthalmos with other malformations; FRAS1-Related Fraser Syndrome; FRASRS1
 
Gene (location): FRAS1 (4q21.21)
 
Monarch Initiative: MONDO:0054737
OMIM®: 219000

Definition

Fraser syndrome is an autosomal recessive malformation disorder characterized by cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract (summary by van Haelst et al., 2008). Genetic Heterogeneity of Fraser Syndrome Fraser syndrome-2 (FRASRS2) is caused by mutation in the FREM2 gene (608945) on chromosome 13q13, and Fraser syndrome-3 (FRASRS3; 617667) is caused by mutation in the GRIP1 gene (604597) on chromosome 12q14. See Bowen syndrome (211200) for a comparable but probably distinct syndrome of multiple congenital malformations. [from OMIM]

Additional description

From MedlinePlus Genetics
Fraser syndrome is a rare disorder that affects development starting before birth. Characteristic features of this condition include eyes that are completely covered by skin and usually malformed (cryptophthalmos), fusion of the skin between the fingers and toes (cutaneous syndactyly), and abnormalities of the genitalia and the urinary tract (genitourinary anomalies). Other tissues and organs can also be affected. Depending on the severity of the signs and symptoms, Fraser syndrome can be fatal before or shortly after birth; less severely affected individuals can live into childhood or adulthood.

Cryptophthalmos is the most common abnormality in people with Fraser syndrome. Both eyes are usually completely covered by skin, but in some cases, only one eye is covered or one or both eyes are partially covered. In cryptophthalmos, the eyes can also be malformed; for example, the eyeballs may be fused to the skin covering them, or they may be small (microphthalmia) or missing (anophthalmia). Eye abnormalities typically lead to impairment or loss of vision in people with Fraser syndrome. Affected individuals can have other problems related to abnormal eye development, including missing eyebrows or eyelashes or a patch of hair extending from the side hairline to the eyebrow.

Cutaneous syndactyly typically occurs in both the hands and the feet in Fraser syndrome. In most people with this feature, the skin between the middle three fingers and toes are fused, but the other digits can also be involved. Other abnormalities of the hands and feet can occur in people with Fraser syndrome.

Individuals with Fraser syndrome can have abnormalities of the genitalia, such as an enlarged clitoris in females or undescended testes (cryptorchidism) in males. Some affected individuals have external genitalia that do not appear clearly female or male.

The most common urinary tract abnormality in Fraser syndrome is the absence of one or both kidneys (renal agenesis). Affected individuals can have other kidney problems or abnormalities of the bladder and other parts of the urinary tract.

A variety of other signs and symptoms can be involved in Fraser syndrome, including heart malformations or abnormalities of the voicebox (larynx) or other parts of the respiratory tract. Some affected individuals have facial abnormalities, including ear or nose abnormalities or an opening in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate).  https://medlineplus.gov/genetics/condition/fraser-syndrome

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).
Clitoral hypertrophy
MedGen UID:
57848
Concept ID:
C0156394
Finding
Hypertrophy of the clitoris.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Bicornuate uterus
MedGen UID:
78599
Concept ID:
C0266387
Congenital Abnormality
The presence of a bicornuate uterus.
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Vaginal atresia
MedGen UID:
232948
Concept ID:
C1321884
Congenital Abnormality
Congenital occlusion of the vagina or adhesion of the walls of the vagina causing occlusion.
Renal hypoplasia/aplasia
MedGen UID:
387822
Concept ID:
C1857453
Finding
Absence or underdevelopment of the kidney.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Aplasia/Hypoplasia of the phalanges of the hand
MedGen UID:
341279
Concept ID:
C1848670
Finding
Small or missing phalangeal bones of the fingers of the hand.
Aplasia/Hypoplasia of the thumb
MedGen UID:
465975
Concept ID:
C3179508
Finding
Hypoplastic/small or absent thumb.
Cutaneous finger syndactyly
MedGen UID:
866898
Concept ID:
C4021254
Congenital Abnormality
A soft tissue continuity in the A/P axis between two fingers that extends distally to at least the level of the proximal interphalangeal joints, or a soft tissue continuity in the A/P axis between two fingers that lies significantly distal to the flexion crease that overlies the metacarpophalangeal joint of the adjacent fingers.
Abnormal heart morphology
MedGen UID:
6748
Concept ID:
C0018798
Congenital Abnormality
Any structural anomaly of the heart.
Abnormal umbilicus morphology
MedGen UID:
340299
Concept ID:
C1849338
Anatomical Abnormality
An abnormality of the structure or appearance of the umbilicus.
Abnormality of the anus
MedGen UID:
870868
Concept ID:
C4025329
Anatomical Abnormality
Abnormality of the anal canal.
Abnormal small intestine morphology
MedGen UID:
871236
Concept ID:
C4025717
Anatomical Abnormality
A structural abnormality of the small intestine.
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Atresia of the external auditory canal
MedGen UID:
78613
Concept ID:
C0266597
Congenital Abnormality
Absence or failure to form of the external auditory canal.
Abnormal pinna morphology
MedGen UID:
167800
Concept ID:
C0857379
Congenital Abnormality
An abnormality of the pinna, which is also referred to as the auricle or external ear.
Cupped ear
MedGen UID:
335186
Concept ID:
C1845447
Congenital Abnormality
Laterally protruding ear that lacks antihelical folding (including absence of inferior and superior crura).
Abnormal middle ear morphology
MedGen UID:
387824
Concept ID:
C1857456
Anatomical Abnormality
An abnormality of the morphology or structure of the middle ear.
Hypoplastic superior helix
MedGen UID:
355438
Concept ID:
C1865305
Finding
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Myelomeningocele
MedGen UID:
7538
Concept ID:
C0025312
Congenital Abnormality
Protrusion of the meninges and portions of the spinal cord through a defect of the vertebral column.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Abnormal cortical gyration
MedGen UID:
343457
Concept ID:
C1856019
Anatomical Abnormality
An abnormality of the gyri (i.e., the ridges) of the cerebral cortex of the brain.
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.
Encephalocele
MedGen UID:
1646412
Concept ID:
C4551722
Congenital Abnormality
A neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull.
Wide pubic symphysis
MedGen UID:
387763
Concept ID:
C1857190
Finding
Abnormally increased width of the pubic symphysis is the midline cartilaginous joint uniting the superior rami of the left and right pubic bones.
Aplasia/Hypoplasia of the sternum
MedGen UID:
870542
Concept ID:
C4024990
Finding
Calvarial skull defect
MedGen UID:
871299
Concept ID:
C4025787
Anatomical Abnormality
A localized defect in the bone of the skull resulting from abnormal embryological development. The defect is covered by normal skin. In some cases, skull x-rays have shown underlying lytic bone lesions which have closed before the age of one year.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Laryngeal stenosis
MedGen UID:
7274
Concept ID:
C0023075
Pathologic Function
Stricture or narrowing of the larynx that may be associated with symptoms of respiratory difficulty depending on the degree of laryngeal narrowing.
Subglottic stenosis
MedGen UID:
68668
Concept ID:
C0238441
Anatomical Abnormality
Laryngeal atresia
MedGen UID:
78572
Concept ID:
C0265756
Congenital Abnormality
Congenital absence of the lumen of the larynx. Laryngeal atresia is a rare condition. If the laryngeal opening fails to develop, fluid secreted by the lungs cannot be expelled. In a fetus with laryngeal atresia, the lungs are either normal or hyperplastic, not hypoplastic. Mortality is reported as 100%. At obstetric US examination, views of the fetal neck demonstrate a dilated trachea filled with trapped fluid. Views of the fetal chest show enlarged, hyperechoic lungs, with dilated fluid-filled bronchi. Fetal ascites is usually present.
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Laryngeal web
MedGen UID:
84297
Concept ID:
C0281890
Disease or Syndrome
A membrane-like structure that extends across the laryngeal lumen close to the level of the vocal cords.
Abnormal thymus morphology
MedGen UID:
852464
Concept ID:
C0262650
Finding
Abnormality of the thymus, an organ located in the upper anterior portion of the chest cavity just behind the sternum and whose main function is to provide an environment for T lymphocyte maturation.
Severe T-cell immunodeficiency
MedGen UID:
870751
Concept ID:
C4025208
Disease or Syndrome
A primary immune deficiency that is characterized by defects or deficiencies of T-lymphocytes that causes specific susceptibility to intracellular micro-organisms.
Cleft upper lip
MedGen UID:
40327
Concept ID:
C0008924
Congenital Abnormality
A gap or groove in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.
Dental malocclusion
MedGen UID:
9869
Concept ID:
C0024636
Anatomical Abnormality
Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.
Dental crowding
MedGen UID:
11850
Concept ID:
C0040433
Finding
Changes in alignment of teeth in the dental arch
Cryptophthalmia
MedGen UID:
81386
Concept ID:
C0311249
Congenital Abnormality
Cryptophthalmos is a condition of total absence of eyelids and the skin of forehead is continuous with that of cheek, in which the eyeball is completely concealed by the skin, which is stretched over the orbital cavity.
Wide nose
MedGen UID:
140869
Concept ID:
C0426421
Finding
Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.
Absent eyebrow
MedGen UID:
98133
Concept ID:
C0431448
Congenital Abnormality
Absence of the eyebrow.
Choanal stenosis
MedGen UID:
108427
Concept ID:
C0584837
Finding
Abnormal narrowing of the choana (the posterior nasal aperture).
Tessier cleft
MedGen UID:
146898
Concept ID:
C0685787
Congenital Abnormality
A congenital malformation with a cleft (gap or opening) in the face.
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
Underdeveloped nasal alae
MedGen UID:
322332
Concept ID:
C1834055
Congenital Abnormality
Thinned, deficient, or excessively arched ala nasi.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Cleft ala nasi
MedGen UID:
336715
Concept ID:
C1844537
Finding
The presence of a notch in the margin of the ala nasi.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Difficulty in tongue movements
MedGen UID:
377897
Concept ID:
C1853406
Finding
Extension of hair growth on temples to lateral eyebrow
MedGen UID:
346590
Concept ID:
C1857455
Finding
A pattern of hair growth in which there is hair extending from the temples to the lateral eyebrows.
Upper eyelid coloboma
MedGen UID:
350283
Concept ID:
C1863872
Disease or Syndrome
A short discontinuity of the margin of the upper eyelid.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Malformed lacrimal duct
MedGen UID:
870314
Concept ID:
C4024757
Anatomical Abnormality
Congenital malformation of the lacrimal duct associated with incomplete development of the bony nasolacrimal canal or craniofacial anomalies.
Lacrimal duct aplasia
MedGen UID:
870330
Concept ID:
C4024773
Congenital Abnormality
A congenital defect resulting in absence of the lacrimal duct.
Midline nasal groove
MedGen UID:
870949
Concept ID:
C4025412
Anatomical Abnormality
An abnormal groove on the midline of the nose that may extend to the nasal tip.
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.
Absent eyelashes
MedGen UID:
334299
Concept ID:
C1843005
Congenital Abnormality
Lack of eyelashes.
Enlarged fetal lungs
MedGen UID:
1053128
Concept ID:
CN377445
Finding
The size (volume) of the lungs of a fetus above the upper limit of normal for the gestational age.
Wide intermamillary distance
MedGen UID:
473489
Concept ID:
C1827524
Finding
A larger than usual distance between the left and right nipple.
Anophthalmia
MedGen UID:
314
Concept ID:
C0003119
Congenital Abnormality
Absence of the globe or eyeball.
Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
A reduction of corneal clarity.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation.
Bilateral microphthalmos
MedGen UID:
334420
Concept ID:
C1843496
Congenital Abnormality
A developmental anomaly characterized by abnormal smallness of both eyes.

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