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Fryns syndrome(FRNS)

MedGen UID:
65088
Concept ID:
C0220730
Disease or Syndrome
Synonyms: Diaphragmatic hernia, abnormal face, and distal limb anomalies; FRNS; Moerman Van den berghe Fryns syndrome
SNOMED CT: Fryns syndrome (702432006); Diaphragmatic hernia, abnormal face and distal limb anomalies (702432006)
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).
 
Monarch Initiative: MONDO:0009253
OMIM®: 229850
Orphanet: ORPHA2059

Disease characteristics

Excerpted from the GeneReview: Fryns Syndrome
Fryns syndrome is characterized by diaphragmatic defects (diaphragmatic hernia, eventration, hypoplasia, or agenesis); characteristic facial appearance (coarse facies, wide-set eyes, a wide and depressed nasal bridge with a broad nasal tip, long philtrum, low-set and anomalous ears, tented vermilion of the upper lip, wide mouth, and a small jaw); short distal phalanges of the fingers and toes (the nails may also be small); pulmonary hypoplasia; and associated anomalies (polyhydramnios, cloudy corneas and/or microphthalmia, orofacial clefting, renal dysplasia / renal cortical cysts, and/or malformations involving the brain, cardiovascular system, gastrointestinal system, and/or genitalia). Survival beyond the neonatal period is rare. Data on postnatal growth and psychomotor development are limited; however, severe developmental delay and intellectual disability are common. [from GeneReviews]
Authors:
Anne Slavotinek   view full author information

Additional descriptions

From OMIM
Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome that is usually lethal in the neonatal period (Alessandri et al., 2005). Fryns (1987) reviewed the syndrome. Also see Tonne-Kalscheuer syndrome (300978), an X-linked disorder with overlapping features.  http://www.omim.org/entry/229850
From MedlinePlus Genetics
Fryns syndrome is a condition that affects the development of many parts of the body. The features of this disorder vary widely among affected individuals and overlap with the signs and symptoms of several other disorders. These factors can make Fryns syndrome difficult to diagnose.

Most people with Fryns syndrome have a defect in the muscle that separates the abdomen from the chest cavity (the diaphragm). The most common defect is a congenital diaphragmatic hernia, which is a hole in the diaphragm that develops before birth. This hole allows the stomach and intestines to move into the chest and crowd the heart and lungs. As a result, the lungs often do not develop properly (pulmonary hypoplasia), which can cause life-threatening breathing difficulties in affected infants.

Other major signs of Fryns syndrome include abnormalities of the fingers and toes and distinctive facial features. The tips of the fingers and toes tend to be underdeveloped, resulting in a short and stubby appearance with small or absent nails. Most affected individuals have several unusual facial features, including widely spaced eyes (hypertelorism), a broad and flat nasal bridge, a thick nasal tip, a wide space between the nose and upper lip (a long philtrum), a large mouth (macrostomia), and a small chin (micrognathia). Many also have low-set and abnormally shaped ears.

Several additional features have been reported in people with Fryns syndrome. These include small eyes (microphthalmia), clouding of the clear outer covering of the eye (the cornea), and an opening in the roof of the mouth (cleft palate) with or without a split in the lip (cleft lip). Fryns syndrome can also affect the development of the brain, cardiovascular system, gastrointestinal system, kidneys, and genitalia.

Most people with Fryns syndrome die before birth or in early infancy from pulmonary hypoplasia caused by a congenital diaphragmatic hernia. However, a few affected individuals have lived into childhood. Many of these children have had severe developmental delay and intellectual disability.  https://medlineplus.gov/genetics/condition/fryns-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).
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Ureteral duplication
MedGen UID:
66380
Concept ID:
C0221365
Congenital Abnormality
A developmental anomaly characterized by the presence of two, instead of one, ureter connecting a kidney to the bladder.
Bicornuate uterus
MedGen UID:
78599
Concept ID:
C0266387
Congenital Abnormality
The presence of a bicornuate uterus.
Bifid scrotum
MedGen UID:
90968
Concept ID:
C0341787
Congenital Abnormality
Midline indentation or cleft of the scrotum.
Renal agenesis
MedGen UID:
154237
Concept ID:
C0542519
Congenital Abnormality
Agenesis, that is, failure of the kidney to develop during embryogenesis and development.
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.
Shawl scrotum
MedGen UID:
388088
Concept ID:
C1858539
Congenital Abnormality
Superior margin of the scrotum superior to the base of the penis.
Renal cyst
MedGen UID:
854361
Concept ID:
C3887499
Disease or Syndrome
A fluid filled sac in the kidney.
Congenital vertical talus
MedGen UID:
66821
Concept ID:
C0240912
Congenital Abnormality
Congenital vertical talus (CVT), also known as 'rocker-bottom foot' deformity, is a dislocation of the talonavicular joint characterized by vertical orientation of the talus with a rigid dorsal dislocation of the navicular, equinus deformity of the calcaneus, abduction deformity of the forefoot, and contracture of the soft tissues of the hind- and mid-foot. This condition is usually associated with multiple other congenital deformities and only rarely is an isolated deformity with familial occurrence (summary by Levinsohn et al., 2004). The condition is transmitted in an autosomal dominant pattern of inheritance, and sometimes shows incomplete penetrance and variable expressivity. There may be a broad spectrum of deformities, including flatfoot, talipes equinovarus (TEV or clubfoot), cavus foot, metatarsus adductus, and even hypoplasia of the tibia (summary by Dobbs et al., 2006).
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Short thumb
MedGen UID:
98469
Concept ID:
C0431890
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the thumb.
Short distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Proximal placement of thumb
MedGen UID:
356033
Concept ID:
C1865572
Finding
Proximal mislocalization of the thumb.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Large for gestational age
MedGen UID:
341215
Concept ID:
C1848395
Finding
The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age.
Imperforate anus
MedGen UID:
1997
Concept ID:
C0003466
Congenital Abnormality
Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract.
Esophageal atresia
MedGen UID:
4545
Concept ID:
C0014850
Congenital Abnormality
A developmental defect resulting in complete obliteration of the lumen of the esophagus such that the esophagus ends in a blind pouch rather than connecting to the stomach.
Meckel diverticulum
MedGen UID:
9917
Concept ID:
C0025037
Congenital Abnormality
Meckel's diverticulum is a congenital diverticulum located in the distal ileum.
Intestinal malrotation
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis.
Duodenal atresia
MedGen UID:
75602
Concept ID:
C0266174
Congenital Abnormality
A developmental defect resulting in complete obliteration of the duodenal lumen, that is, an abnormal closure of the duodenum.
Ectopic pancreatic tissue
MedGen UID:
203053
Concept ID:
C0994638
Finding
The presence of pancreatic tissue outside the normal pancreas, in many cases along the foregut and proximal midgut.
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.
Abnormal helix morphology
MedGen UID:
344782
Concept ID:
C1856660
Anatomical Abnormality
An abnormality of the helix. The helix is the outer rim of the ear that extends from the insertion of the ear on the scalp (root) to the termination of the cartilage at the earlobe.
Aganglionic megacolon
MedGen UID:
5559
Concept ID:
C0019569
Disease or Syndrome
The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid (Amiel et al., 2008). Total colonic aganglionosis and total intestinal HSCR also occur. Genetic Heterogeneity of Hirschsprung Disease Several additional loci for isolated Hirschsprung disease have been mapped. HSCR2 (600155) is associated with variation in the EDNRB gene (131244) on 13q22; HSCR3 (613711) is associated with variation in the GDNF gene (600837) on 5p13; HSCR4 (613712) is associated with variation in the EDN3 gene (131242) on 20q13; HSCR5 (600156) maps to 9q31; HSCR6 (606874) maps to 3p21; HSCR7 (606875) maps to 19q12; HSCR8 (608462) maps to 16q23; and HSCR9 (611644) maps to 4q31-q32. HSCR also occurs as a feature of several syndromes including the Waardenburg-Shah syndrome (277580), Mowat-Wilson syndrome (235730), Goldberg-Shprintzen syndrome (609460), and congenital central hypoventilation syndrome (CCHS; 209880). Whereas mendelian modes of inheritance have been described for syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance. The development of surgical procedures decreased mortality and morbidity, which allowed the emergence of familial cases. HSCR occurs as an isolated trait in 70% of patients, is associated with chromosomal anomaly in 12% of cases, and occurs with additional congenital anomalies in 18% of cases (summary by Amiel et al., 2008).
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Arrhinencephaly
MedGen UID:
36258
Concept ID:
C0078982
Congenital Abnormality
A defect of development of the brain characterized by congenital absence of the part of the brain that includes the olfactory bulbs, tracts, and other structures associated with the sense of smell.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Hypoplasia of the optic tract
MedGen UID:
347279
Concept ID:
C1856654
Finding
Hypoplasia of olfactory tract
MedGen UID:
347280
Concept ID:
C1856655
Finding
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.
Dandy-Walker syndrome
MedGen UID:
4150
Concept ID:
C0010964
Disease or Syndrome
Dandy-Walker malformation is defined by hypoplasia and upward rotation of the cerebellar vermis and cystic dilation of the fourth ventricle. Affected individuals often have motor deficits such as delayed motor development, hypotonia, and ataxia; about half have mental retardation and some have hydrocephalus. DWM is a heterogeneous disorder. The low empiric recurrence risk of approximately 1 to 2% for nonsyndromic DWM suggests that mendelian inheritance is unlikely (summary by Murray et al., 1985).
Joint contracture of the hand
MedGen UID:
56382
Concept ID:
C0158113
Finding
Contractures of one ore more joints of the hands meaning chronic loss of joint motion due to structural changes in non-bony tissue.
Thin ribs
MedGen UID:
98095
Concept ID:
C0426818
Finding
Ribs with a reduced diameter.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
Congenital omphalocele
MedGen UID:
162756
Concept ID:
C0795690
Congenital Abnormality
An omphalocele is an abdominal wall defect limited to an open umbilical ring, and is characterized by the herniation of membrane-covered internal organs into the open base of the umbilical cord. Omphalocele is distinguished from gastroschisis (230750), in which the abdominal wall defect is located laterally to a normally closed umbilical ring with herniation of organs that are uncovered by membranes (summary by Bugge, 2010). On the basis of clinical manifestations, epidemiologic characteristics, and the presence of additional malformations, Yang et al. (1992) concluded that omphalocele and gastroschisis are casually and pathogenetically distinct abdominal wall defects. Omphalocele can be a feature of genetic disorders, such as Beckwith-Wiedemann syndrome (130650) and the Shprintzen-Goldberg syndrome (182210).
Thoracic hypoplasia
MedGen UID:
373339
Concept ID:
C1837482
Congenital Abnormality
Microretrognathia
MedGen UID:
326907
Concept ID:
C1839546
Finding
A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly.
Broad ribs
MedGen UID:
336390
Concept ID:
C1848654
Finding
Increased width of ribs
Aplasia of the left hemidiaphragm
MedGen UID:
1680550
Concept ID:
C5194758
Finding
Congenital absence of the left half of the diaphragm.
Chylothorax
MedGen UID:
40305
Concept ID:
C0008733
Disease or Syndrome
Accumulation of excessive amounts of lymphatic fluid (chyle) in the pleural cavity.
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.
Polysplenia
MedGen UID:
383959
Concept ID:
C1856659
Congenital Abnormality
Polysplenia is a congenital disease manifested by multiple small accessory spleens.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Congenital Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
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.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Tented upper lip vermilion
MedGen UID:
326574
Concept ID:
C1839767
Finding
Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Broad neck
MedGen UID:
344099
Concept ID:
C1853638
Finding
Increased side-to-side width of the neck.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Narrow palpebral fissure
MedGen UID:
382506
Concept ID:
C2675021
Finding
Reduction in the vertical distance between the upper and lower eyelids.
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).
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.
Anonychia
MedGen UID:
120563
Concept ID:
C0265998
Congenital Abnormality
Congenital anonychia is defined as the absence of fingernails and toenails. Anonychia and its milder phenotypic variant, hyponychia, usually occur as a feature of genetic syndromes, in association with significant skeletal and limb anomalies. Isolated nonsyndromic congenital anonychia/hyponychia is a rare entity that usually follows autosomal recessive inheritance with variable expression, even within a given family. The nail phenotypes observed range from no nail field to a nail field of reduced size with an absent or rudimentary nail (summary by Bruchle et al., 2008). This form of nail disorder is referred to here as nonsyndromic congenital nail disorder-4 (NDNC4). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
Prominent fingertip pads
MedGen UID:
322758
Concept ID:
C1835807
Finding
A soft tissue prominence of the ventral aspects of the fingertips. The term "persistent fetal fingertip pads" is often used as a synonym, but should better not be used because it implies knowledge of history of the patient which often does not exist.
Facial hirsutism
MedGen UID:
337950
Concept ID:
C1850041
Finding
Excess facial hair.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
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).
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Opacification of the corneal stroma
MedGen UID:
602191
Concept ID:
C0423250
Finding
Reduced transparency of the stroma of cornea.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFryns syndrome
Follow this link to review classifications for Fryns syndrome in Orphanet.

Professional guidelines

PubMed

Loong L, Tardivo A, Knaus A, Hashim M, Pagnamenta AT, Alt K, Böhrer-Rabel H, Caro-Llopis A, Cole T, Distelmaier F, Edery P, Ferreira CR, Jezela-Stanek A, Kerr B, Kluger G, Krawitz PM, Kuhn M, Lemke JR, Lesca G, Lynch SA, Martinez F, Maxton C, Mierzewska H, Monfort S, Nicolai J, Orellana C, Pal DK, Płoski R, Quarrell OW, Rosello M, Rydzanicz M, Sabir A, Śmigiel R, Stegmann APA, Stewart H, Stumpel C, Szczepanik E, Tzschach A, Wolfe L, Taylor JC, Murakami Y, Kinoshita T, Bayat A, Kini U
Genet Med 2023 Jan;25(1):37-48. Epub 2022 Nov 2 doi: 10.1016/j.gim.2022.09.007. PMID: 36322149
Bétrémieux P, Lionnais S, Beuchée A, Pladys P, Le Bouar G, Pasquier L, Loeuillet-Olivo L, Azzis O, Milon J, Wodey E, Frémond B, Odent S, Poulain P
Prenat Diagn 2002 Nov;22(11):988-94. doi: 10.1002/pd.454. PMID: 12424762
Van Wymersch D, Favre R, Gasser B
Fetal Diagn Ther 1996 Sep-Oct;11(5):335-40. doi: 10.1159/000264336. PMID: 8894628

Recent clinical studies

Etiology

Loong L, Tardivo A, Knaus A, Hashim M, Pagnamenta AT, Alt K, Böhrer-Rabel H, Caro-Llopis A, Cole T, Distelmaier F, Edery P, Ferreira CR, Jezela-Stanek A, Kerr B, Kluger G, Krawitz PM, Kuhn M, Lemke JR, Lesca G, Lynch SA, Martinez F, Maxton C, Mierzewska H, Monfort S, Nicolai J, Orellana C, Pal DK, Płoski R, Quarrell OW, Rosello M, Rydzanicz M, Sabir A, Śmigiel R, Stegmann APA, Stewart H, Stumpel C, Szczepanik E, Tzschach A, Wolfe L, Taylor JC, Murakami Y, Kinoshita T, Bayat A, Kini U
Genet Med 2023 Jan;25(1):37-48. Epub 2022 Nov 2 doi: 10.1016/j.gim.2022.09.007. PMID: 36322149
Shah A, Bapna M, Al-Saif H, Li R, Couser NL
Ophthalmic Genet 2022 Feb;43(1):126-129. Epub 2021 Oct 20 doi: 10.1080/13816810.2021.1989601. PMID: 34670449
Bayat A, Knaus A, Pendziwiat M, Afenjar A, Barakat TS, Bosch F, Callewaert B, Calvas P, Ceulemans B, Chassaing N, Depienne C, Endziniene M, Ferreira CR, Moura de Souza CF, Freihuber C, Ganesan S, Gataullina S, Guerrini R, Guerrot AM, Hansen L, Jezela-Stanek A, Karsenty C, Kievit A, Kooy FR, Korff CM, Kragh Hansen J, Larsen M, Layet V, Lesca G, McBride KL, Meuwissen M, Mignot C, Montomoli M, Moore H, Naudion S, Nava C, Nougues MC, Parrini E, Pastore M, Schelhaas JH, Skinner S, Szczałuba K, Thomas A, Thomassen M, Tranebjaerg L, van Slegtenhorst M, Wolfe LA, Lal D, Gardella E, Bomme Ousager L, Brünger T, Helbig I, Krawitz P, Møller RS
Epilepsia 2020 Jun;61(6):1142-1155. Epub 2020 May 26 doi: 10.1111/epi.16545. PMID: 32452540
Lin AE, Pober BR, Mullen MP, Slavotinek AM
Am J Med Genet A 2005 Dec 15;139(3):186-93. doi: 10.1002/ajmg.a.31023. PMID: 16283673
Enns GM, Cox VA, Goldstein RB, Gibbs DL, Harrison MR, Golabi M
Am J Med Genet 1998 Sep 23;79(3):215-25. PMID: 9788565

Diagnosis

Graham JM Jr, Schwartz CE
Am J Med Genet A 2013 Nov;161A(11):2734-40. Epub 2013 Oct 10 doi: 10.1002/ajmg.a.36183. PMID: 24123922Free PMC Article
Solomon BD
Orphanet J Rare Dis 2011 Aug 16;6:56. doi: 10.1186/1750-1172-6-56. PMID: 21846383Free PMC Article
Van Buggenhout G, Fryns JP
Orphanet J Rare Dis 2006 Jul 10;1:26. doi: 10.1186/1750-1172-1-26. PMID: 16831221Free PMC Article
Lin AE, Pober BR, Mullen MP, Slavotinek AM
Am J Med Genet A 2005 Dec 15;139(3):186-93. doi: 10.1002/ajmg.a.31023. PMID: 16283673
Slavotinek AM
Am J Med Genet A 2004 Feb 1;124A(4):427-33. doi: 10.1002/ajmg.a.20381. PMID: 14735597

Therapy

Maia N, Ibarluzea N, Misra-Isrie M, Koboldt DC, Marques I, Soares G, Santos R, Marcelis CLM, Keski-Filppula R, Guitart M, Gabau Vila E, Lehman A, Hickey S, Mori M, Terhal P, Valenzuela I, Lasa-Aranzasti A, Cueto-González AM, Chhouk BH, Yeh RC, Neil JE, Abu-Libde B, Kleefstra T, Elting MW, Császár A, Kárteszi J, Bessenyei B, van Bokhoven H, Jorge P, van Hagen JM, de Brouwer APM
Am J Med Genet A 2023 Jan;191(1):135-143. Epub 2022 Oct 22 doi: 10.1002/ajmg.a.63004. PMID: 36271811Free PMC Article
Parisi MA, Zayed H, Slavotinek AM, Rutledge JC
Am J Med Genet A 2009 Jun;149A(6):1237-40. doi: 10.1002/ajmg.a.32684. PMID: 19449404Free PMC Article
Gadow EC, Lippold S, Serafin E, Salgado LJ, Garcia C, Prudent L
Prenat Diagn 1994 Aug;14(8):673-6. doi: 10.1002/pd.1970140806. PMID: 7991509

Prognosis

Loong L, Tardivo A, Knaus A, Hashim M, Pagnamenta AT, Alt K, Böhrer-Rabel H, Caro-Llopis A, Cole T, Distelmaier F, Edery P, Ferreira CR, Jezela-Stanek A, Kerr B, Kluger G, Krawitz PM, Kuhn M, Lemke JR, Lesca G, Lynch SA, Martinez F, Maxton C, Mierzewska H, Monfort S, Nicolai J, Orellana C, Pal DK, Płoski R, Quarrell OW, Rosello M, Rydzanicz M, Sabir A, Śmigiel R, Stegmann APA, Stewart H, Stumpel C, Szczepanik E, Tzschach A, Wolfe L, Taylor JC, Murakami Y, Kinoshita T, Bayat A, Kini U
Genet Med 2023 Jan;25(1):37-48. Epub 2022 Nov 2 doi: 10.1016/j.gim.2022.09.007. PMID: 36322149
Bayat A, Knaus A, Pendziwiat M, Afenjar A, Barakat TS, Bosch F, Callewaert B, Calvas P, Ceulemans B, Chassaing N, Depienne C, Endziniene M, Ferreira CR, Moura de Souza CF, Freihuber C, Ganesan S, Gataullina S, Guerrini R, Guerrot AM, Hansen L, Jezela-Stanek A, Karsenty C, Kievit A, Kooy FR, Korff CM, Kragh Hansen J, Larsen M, Layet V, Lesca G, McBride KL, Meuwissen M, Mignot C, Montomoli M, Moore H, Naudion S, Nava C, Nougues MC, Parrini E, Pastore M, Schelhaas JH, Skinner S, Szczałuba K, Thomas A, Thomassen M, Tranebjaerg L, van Slegtenhorst M, Wolfe LA, Lal D, Gardella E, Bomme Ousager L, Brünger T, Helbig I, Krawitz P, Møller RS
Epilepsia 2020 Jun;61(6):1142-1155. Epub 2020 May 26 doi: 10.1111/epi.16545. PMID: 32452540
Solomon BD
Orphanet J Rare Dis 2011 Aug 16;6:56. doi: 10.1186/1750-1172-6-56. PMID: 21846383Free PMC Article
Van Buggenhout G, Fryns JP
Orphanet J Rare Dis 2006 Jul 10;1:26. doi: 10.1186/1750-1172-1-26. PMID: 16831221Free PMC Article
Alessandri L, Brayer C, Attali T, Samperiz S, Tiran-Rajaofera I, Ramful D, Pilorget H
Genet Couns 2005;16(4):363-70. PMID: 16440878

Clinical prediction guides

Loong L, Tardivo A, Knaus A, Hashim M, Pagnamenta AT, Alt K, Böhrer-Rabel H, Caro-Llopis A, Cole T, Distelmaier F, Edery P, Ferreira CR, Jezela-Stanek A, Kerr B, Kluger G, Krawitz PM, Kuhn M, Lemke JR, Lesca G, Lynch SA, Martinez F, Maxton C, Mierzewska H, Monfort S, Nicolai J, Orellana C, Pal DK, Płoski R, Quarrell OW, Rosello M, Rydzanicz M, Sabir A, Śmigiel R, Stegmann APA, Stewart H, Stumpel C, Szczepanik E, Tzschach A, Wolfe L, Taylor JC, Murakami Y, Kinoshita T, Bayat A, Kini U
Genet Med 2023 Jan;25(1):37-48. Epub 2022 Nov 2 doi: 10.1016/j.gim.2022.09.007. PMID: 36322149
Winter-Paquette LM, Al Suwaidi HH, Sajjad Y, Bricker L
Eur J Med Genet 2022 May;65(5):104501. Epub 2022 Apr 1 doi: 10.1016/j.ejmg.2022.104501. PMID: 35378319
Geniş B, Şahin F, Coşar B
Turk Psikiyatri Derg 2020 Fall;31(3):216-220. doi: 10.5080/u23940. PMID: 32978958
Prontera P, Ottaviani V, Rogaia D, Isidori I, Mencarelli A, Malerba N, Cocciadiferro D, Rolph P, Stangoni G, Vulto-van Silfhout A, Merla G
Am J Med Genet A 2016 Sep;170(9):2377-82. Epub 2016 Jun 17 doi: 10.1002/ajmg.a.37805. PMID: 27312080
Alkuraya FS, Lin AE, Irons MB, Kimonis VE
Am J Med Genet A 2005 Jan 15;132A(2):226-30. doi: 10.1002/ajmg.a.30423. PMID: 15580636

Recent systematic reviews

Shah A, Bapna M, Al-Saif H, Li R, Couser NL
Ophthalmic Genet 2022 Feb;43(1):126-129. Epub 2021 Oct 20 doi: 10.1080/13816810.2021.1989601. PMID: 34670449

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