18q syndrome is a rare chromosomal anomaly where there is deletion of part of the long arm of chromosome 18. Associated symptoms and findings vary widely, as does their severity. Characteristic features include short stature, mental retardation and hypotonia, facial and distal skeletal abnorma...
The 22q11.2 deletion syndrome (also known as the DiGeorge syndrome or velocardiofacial syndrome) is a syndrome where a small portion of the chromosome 22 is lost and results in a variable but recognisable pattern of physical and behavioral features.
The estimated incidence is at ~...
Aase-Smith syndrome is an extremely rare congenital disorder.
congenital hypoplastic anaemia - fetal anaemia
cleft lip, cleft palate
hydrocephalus (due to Dandy-Walker anomaly)
The Adams-Oliver syndrome (AOS) is a rare disorder characterised by aplasia cutis congenita (missing hair and/or skin) and variable degrees of terminal transverse limb defects.
polymicrogyria: can be associated with a variant of Adams-Oliver syndrome 3
Aicardi syndrome is a rare severe developmental disorder. It results from an X-linked genetic defect that is fatal in males and therefore only manifests in females (except for rare 47-XXY cases).
The typical presentation in infancy is with a triad of:
infantile spasms: salaa...
Alagille syndrome (AGS) is a congenital genetic multi-system disorder.
Infants typically present with symptoms relating to the liver where is it one of the most common causes of hereditary cholestasis.
AGS is inherited in an autosomal fashion with a mutation of...
Apert syndrome (also known as type I acrocephalosyndactyly) is a syndrome that is predominantly characterised by skull and limb malformations.
The estimated incidence is at 1:65-80,000 pregnancies.
Thought to occur from a defect on the fibroblast growth factor receptor...
Asplenia syndrome (also known as right isomerism or Ivemark syndrome) is a type of heterotaxy syndrome.
There is an increased male predilection. Asplenia syndrome is usually diagnosed in neonates.4
In contrast to polysplenia syndrome, most patients die bef...
Barth syndrome (BTHS), also referred to as 3-methylglutaconic aciduria type II is an extremely rare X-linked multi-system disorder that is usually diagnosed in infancy.
It is characterised by:
fetal cardiomyopathy: (dilated fetal cardiomyopathy (DCM) +/- endocardial fibroelastosis (EFE) +/- le...
Bartter syndrome is a rare inherited renal disorder.
Bartter syndrome is characterised by hyperplasia of the juxtaglomerular cells along with:
hypotension or normotension
elevated plasma renin
Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder characterised by a unique set features that can consist of:
macroglossia: most common clinical finding 4
otic dysplasia ref
localised gigantism / macrosomia
Caffey disease or infantile cortical hyperostosis a largely self-limiting disorder which affects infants. It causes bone changes, soft-tissue swelling, and irritability.
A rare variant known as prenatal onset cortical hyperostosis, is also reported and it is severe and fatal.
Children usually ...
Camptodactyly arthropathy coxa vara pericarditis (CACP) syndrome is a rare condition principally characterised by
congenital or early-onset camptodactyly and childhood-onset non-inflammatory arthropathy
coxa vara deformity or other dysplasia associated with progressive hip disease
Caudal regression syndrome (CRS) represents a spectrum of structural defects of the caudal region. Malformations vary from isolated partial agenesis of the coccyx to lumbosacral agenesis.
Caudal regression syndrome is rare, with an estimated incidence of 1:7500-100,000 7,10.
Cerebral hypoventilation syndrome refers to a congenital condition characterised by hypoventilation during sleep with no other abnormalities of cardio-respiratory system. There is a decrease in the depth of breathing .
It is also known as Congenital central hypoventilation syndrome (CCHS) or On...
CHARGE syndrome is an acronym that classically describes a combination head and neck, cardiac, CNS and genitourinary disorders:
H: heart defects (congenital heart disease)
A: atresia (choanal)
R: retardation (mental)
G: genital hypoplasia
E: ear abnormalities/deafness
CHILD syndrome is an acronym for congenital hemidysplasia with ichthyosiform erythroderma and limb defects. It comprises of:
Ch: congenital hemidysplasia
I: ichthyosiform erythroderma
develops at or shortly after birth
unilateral erythema and scaling, with a distinct demarcation in the middl...
Chronic recurrent multifocal osteomyelitis (CRMO) is primarily a diagnosis of exclusion. It is an idiopathic inflammatory disorder of bone seen primarily in children and adolescents.
Females are more commonly affected than males.
The typical clinical pictur...
CLOVE syndrome is an acronym denoting a rare condition consisting of:
Congenital Lipomatous Overgrowth
Abnormalities have a truncal predominance.
Associated findings include:
wide feet and hands
Coffin-Siris syndrome, first described in 1970, is a rare genetic abnormality.
It occurs more frequently in females (with a M:F of ~4:1).
It is thought most likely to relate to a gene on chromosome 7, however its exact location has yet to be determined.
Congenital high airways obstruction syndrome (CHAOS) refers a rare, often lethal, congenital laryngotracheal condition and is primarily characterised by obstruction to the fetal upper airway.
CHAOS can be of three possible types 2:
complete laryngeal atresia without an oesophageal f...
Cowden syndrome, also known as multiple hamartoma syndrome, is characterised by multiple hamartomas throughout the body and increased risk of several cancers.
Type 2 segmental Cowden syndrome is the association of Cowden syndrome with a Cowden naevus, when it is considered a type o...
Crouzon syndrome is rare disorder characterised by premature craniosynostoses.
abnormal calvarial shape: in severe case can give a "cloverleaf skull"
shallow orbits with exopthalmos
mid facial hypoplasia
It carries an autosomal...
Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy (SMEI), is a rare form of epilepsy usually presenting in the first 1-2 years of life.
Patients usually present in first six months to one year of life with tonic-clonic seizures in a febrile ch...
Duane radial ray syndrome (DRRS) (also known as the Okihiro syndrome) is a rare an autosomal dominant condition characterized by radial ray defects and a Duane anomaly (a form of strabismus with horizontal gaze palsy).
Dysplasia epiphysealis hemimelica (DEH), also known as Trevor disease, is an extremely rare, non-hereditary disease that is characterised by osteochondromas arising from the epiphyses.
The incidence is estimated at ~1:1,000,000 3. There is a recognised male predilection (M:F = 3:1...
Ectrodactyly-ectrodermal dysplasia-clefting (EEC) syndrome is a rare genetic syndrome that has high clinical variability but typically comprises of the triad of
ectrodactyly +/- syndactyly 1 +/- polydactyly 5
facial clefts: cleft lip and/or palate
Edwards syndrome, also known as trisomy 18, along with Down syndrome (trisomy 21) and Patau syndrome (trisomy13), make up the only three trisomies to be compatible with extra-uterine life in non-mosaic forms, albeit in the case of Edward syndrome only for a week or so.
Eisenmenger syndrome is a complication of an uncorrected high-flow, high-pressure congenital heart anomaly leading to chronic pulmonary arterial hypertension and shunt reversal.
In general, the shunts that lead to Eisenmenger syndrome share are high pressure and high flow 3. As su...
Enchondromatosis, also known as Ollier disease, is a non-hereditary, sporadic, skeletal disorder characterised by multiple enchondromas that are principally located in the metaphyseal regions.
Some authors make a distinction between Ollier disease and enchondromatosis on the basis ...
Fraser syndrome is an extremely rare congenital syndromic anomaly.
The estimated incidence is at around 0.04:10,000 live-born infants and 1:10,000 stillbirths.
The syndromic spectrum can comprises of:
syndactyly: often cutaneous
Glycogen storage disease (GSD) refers to a number of syndromes which are characterised by a defect in synthesis, metabolism or storage of glycogen.
There are many types of GSD:
type I: von Gierke disease
type II: Pompe disease
type III: Cori/Forbe disease
type IV: Andersen diseas...
Goldenhar syndrome (also known as oculo-auriculo-vertebral spectrum (OAVS), Goldenhar-Gorlin syndrome or facio-auriculo-vertebral dysplasia) is a complex congenital anomaly characterised by abnormalities of the ears, eyes and vertebrae.
The estimated incidence is at 1 in 3000-500...
Gomez-Lopez-Hernandez syndrome, also known as cerebellotrigeminal-dermal dysplasia, is a rare phakomatosis characterised by rhombencephalosynapsis, parietal-occipital scalp alopecia, brachycephaly, facial malformations and trigeminal anesthesia.
History and etymology
It is named after Manuel ...
Haemolytic uraemic syndrome (HUS) is a multisystem thrombotic microangiopathic disease characterised by the triad of renal failure, haemolytic anaemia and thrombocytopenia. It is the most common cause of renal failure in infancy and childhood requiring dialysis.
There are two forms of this syn...
The Heiner syndrome is a rare form of primary pulmonary haemosiderosis associated with an allergy to cow's milk.
The syndrome includes
rectal blood loss with hypochromic microcytic anaemia
pulmonary infiltrates (often recurrent)
Hemiconvulsion-hemiplegia epilepsy syndrome (HHE) is a clinical syndrome of infancy or early childhood that is associated with seizures, cerebral hemiatrophy and transient or permanent epilepsy.
It refers to the characteristic holohemispheric global atrophy of one hemisphere, that is independen...
Hemihyperplasia, also known as hemihypertrophy, is asymmetry in size between the right and left of the body, more than can be attributed to normal variation.
Hemihyperplasia is more scientifically correct than hemihyperplasia as the cells are hyperplastic rather than hypertrophied ...
Heterotaxy syndrome or situs ambiguus (also commonly, but etymologically less correctly, spelled situs ambiguous) is a disturbance in the usual left and right distribution of the thoracic and abdominal organs which does not entirely correspond to the complete or partial mirror image.
It occurs ...
Ischiopubic synchondrosis asymmetry is the characteristic enlargement of one of the ischiopubic synchondroses. While it most commonly a normal variant of the developmental process, it is sometimes thought to be syndromic (then called ischiopubic synchondrosis syndrome or van Neck-Odelberg diseas...
Jacobsen syndrome (also known as the chromosome 11q deletion syndrome) is a rare chromosomal anomaly that results from deletion of the terminal region of chromosome 11. It results in intellectual disabilities, a distinctive facial appearance and a variety of physical problems including heart def...
Johanson-Blizzard syndrome is a disorder of ectodermal dysplasia with a wide variability in its manifestations. It is thought to have autosomal recessive inheritance.
There is a wide variability in the clinical presentation, but common features are:
low birth weight
Juberg-Hayward syndrome (JHS) (also knwon as the oro-cranio-digital syndrome) is a rare autosomal recessive syndrome characterised by the association of
cleft lip and palate
minor vertebral and rib anomalies 4
horseshoe kidneys 4
Juvenile polyposis syndrome (familial juvenile polyposis) is one of the polyposis syndromes and consists of hundreds of juvenile polyps.
Presentation in the second decade is most common 2.
Rectal bleeding, bowel obstruction and intussusception are common pr...
Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare polydysplasia that is thought to be more common in Japan.
Estimated incidence of 1:32,000 in Japan. Sporadically seen elsewhere in the world. The reason for the disparity in incidence is controversial.
The cause for t...
Kartagener syndrome is a subset of primary ciliary dyskinesia, an autosomal recessive condition characterised by abnormal ciliary structure and/or function, leading to impaired mucociliary clearance.
The prevalence of primary ciliary dyskinesia is approximately 1 in 12,000-60,000...
Kasabach-Merritt syndrome (also known as haemangioma thrombocytopaenia syndrome) is a rare life-threatening disease found in infant in which a rapidly growing vascular tumour is responsible for thrombocytopaenia, microangiopathic haemolytic anemia and consumptive coagulopathy.
Klinefelter syndrome (KS) is a chromosomal anomaly, which in most cases is characterised by 47 chromosomes instead of the usual 46.
The estimated incidence is 0.15-0.2% of live births.
the testes are normal prior to puberty and small in post pubertal testes...
Klippel-Feil syndrome (KFS) is a complex heterogeneous entity that results in cervical vertebral fusion. Two or more non-segmented cervical vertebrae are usually sufficient for diagnosis.
There is a recognised female predilection 1. KFS has an incidence of 1:40,000-42,000 2.
Labrune syndrome (LS) is a rare condition that consists of a triad of leukoencephalopathy, cerebral calcifications and cysts.
LS is an extremely rare condition, with no more than 10 cases reported in literature 2. The onset occurs from early infancy to adolescence; few cases have...
LEOPARD syndrome (LS) is a rare autosomal dominant hereditary disorder. It is an acronym not the following set of features
L: lentigenes (multiple)
E: ECG conduction abnormalities
O: ocular hypertelorism
P: pulmonary stenosis
A: abnormal genitals
R: retardation of growth
D: deafness (sens...
Lethal omphalocele-cleft palate syndrome is, as the name suggests, characterised by the association of omphalocele and cleft palate.
Prevalence is assumed to be <1 per 1,000,000. It has been postulated that this syndrome is likely to be an autosomal recessive condition.
History and etymol...
McKusick Kaufman syndrome (MKS) is an autosomal recessive multiple malformation syndrome primarily characterised by
hydrometrocolpos - vaginal atresia
congenital heart disease
Meconium plug syndrome refers to a functional colonic obstruction in a newborn due to an obstructing meconium plug. It is usually transient and affects the left colon with meconium plugging the bowel distal to this segment. In this situation it is also termed the small left colon syndrome.
Menkes disease, also known as trichopoliodystrophy or Kinky hair kinky vessel syndrome, is an X-linked recessive disorder that results in a derangement in copper handling. It results in low copper levels and subsequently, deficiency in copper dependant mitochondrial enzymes.
MERRF (myoclonic epilepsy with red ragged fibres) is a rare, multisystem mitochondrial disorder.
Patients usually present in late adolescence or early adulthood with 1,2,3
vision and/or hearing loss
Möbius syndrome is a rare congenital condition characterised by the absence or underdevelopment of the abducens nerve (CN VI) and facial nerve (CN VII) nuclei.
It is estimated that there is ~1 case per 100,000 births 4.
The earliest sign is the inability of...
Morquio syndrome is an autosomal recessive mucopolysaccharidosis (MPS), type IV.
Incidence estimated at ~1:40,000.
Many cases present at ~2 years of age and have normal intelligence. Clinical features:
severe dwarfism (<4 foot)
The mucopolysaccharidoses constitute a group of hereditary disorders having in common an excessive accumulation of mucopolysaccharides secondary to deficiencies in specific enzymes.
Several distinctive types of mucopolysaccharidoses have been described, each with distinctive clinical and radiol...
Norrie disease is a rare X-linked inherited cause of congenital bilateral blindness. It can present with a retinal mass (pseudoglioma) and cataracts. It is associated with developmental delay and hearing loss.
Occipital horn syndrome is a rare X-linked disorder of copper metabolism resulting in connective tissue abnormalities. The Menkes kinky hair syndrome is the severe form of this disease, with patients rarely surviving past 3 years of age. Occipital horn syndrome (also known as X-linked cutis lax...
Patau syndrome (also known as trisomy 13) is considered the 3rd commonest autosomal trisomy.
This along with Down syndrome (T21) and Edward syndrome (T18) are the only three trisomies to be compatible with extrauterine life. However, few infants live more than a few days.
Pepper syndrome is of interest only (the term is not readily used in day-to-day practice), and refers to primary adrenal neuroblastoma with extensive liver metastases 1. In essence, it refers to stage 4S neuroblastoma (see staging of neuroblastoma).
Pre-axial polydactyly refers to polydactyly where the additional digit is towards the first digit of the hand (radial side) or foot (medially).
Pre-axial polydactyly is less common than post-axial polydactyly, with an estimated incidence of 1 in 7000.
Proteus syndrome is a rare congenital, multisystemic, hamartomatous condition characterised by asymmetrical overgrowth of almost any part of the body and a broad spectrum of manifestations. It can affect tissue from any germinal layer. It is suspected to be a genetic condition, but a particular ...
Prune belly syndrome is a rare anomaly comprising a specific constellation of features. It consists of three major findings:
gross ureteric dilatation
anterior abdominal wall underdevelopment (resulting in the "prune belly" appearance)
bilateral undescended testes (cryptorchidism) i...
Raghib syndrome is a rare developmental complex, which consists of persistence of the left superior vena cava along with coronary sinus ostial atresia and atrial septal defect. It has also been associated with other congenital malformations including ventricular septal defects, enlargement of th...
Right middle lobe syndrome refers to chronic right middle lobe collapse, without an obstructing lesion, and usually with associated bronchiectasis.
Right middle lobe syndrome is usually encountered in older adults, with a predilection for women (see Lady Windermere syndrome). It ...
Roberts Syndrome (RBS) (also known as Roberts-SC phocomelia syndrome, pseudothalidomide syndrome, Appelt-Gerken-Lenz syndrome) is rare congenital malformation syndrome. It has an autosomal recessive inheritance.
intrauterine growth restriction (IUGR)
Robin sequence (also called Pierre Robin syndrome or Pierre Robin anamaloid) is a congenital condition characterized by facial abnormalities. Its aetiology has no genetic base, but rather, is reliant on a sequence of events, one following the other.
Robin sequence is the preferred ...
The Sakati-Nyhan syndrome, also known as Sakati-Nyhan-Tisdale syndrome or acrocephalosyndactly type III, is an extremely rare type of acrocephalopolysyndactyly.
Its main features include:
congenital limb abnormalities
congenital heart defects
History and etymology
Scimitar syndrome, also known as hypogenetic lung syndrome, is characterised by a hypoplastic lung that is drained by an anomalous vein into the systemic venous system. It is a type of partial anomalous pulmonary venous return and is one of several findings in congenital pulmonary venolobar synd...
Shone syndrome is characterised by four congenital heart defects, largely multiple left sided obstructions:
supravalvular mitral membrane (SVMM)
subaortic stenosis (membranous or muscular)
parachute mitral valve
coarctation of the aorta
SHORT syndrome refers to an acronym which primarily comprises of the following features:
S: short stature
H: hyperextensibility of joints and/or inguinal hernia
O: ocular depression
R: Rieger anomaly
T: teething delay
In a addition to these there can be numerous associated minor features w...
Sturge-Weber syndrome (SWS), or encephalotrigeminal angiomatosis, is a phakomatosis characterised by facial port wine stains and pial angiomas.
It is part of a wide spectrum of possible phenotypes included in the craniofacial arteriovenous metameric syndrome (CAMS).
It is a rare...
TAR syndrome stands for thrombocytopaenia with absent radius and as the name implies is primarily characterised by the following two features:
absent fetal radii (bilaterally) with the presence of both thumbs
The condition is extremely rare with an estima...
Ulnar dimelia or mirror hand syndrome is a rare congenital anomaly of the upper limb characterized by absence of the radial ray (including thumb), duplication of the ulna and duplication of the ulnar halves of the carpals, metacarpals and phalanges 1.
The embryology of mi...
VACTERL is an acronym that describes a non-random constellation of congenital anomalies. It is not a true syndrome as such and is equivalent to the VATER anomaly.
The estimated incidence is 1 in 10,000-40,000 births 3.
The acronym VACTERL derives from:
V: vertebral an...
VATER (equivalent to VACTERL) is the non-random constellation of a number of congenital anomalies.
V : vertebral anomalies
A : anal atresia
TE : tracheo-oesophageal fistulas
R : radial ray hypoplasia, polydactyly and renal agenesis
The prevalence of at least 3/5 anomalies oc...
The WAGR syndrome stands for:
Wilms tumours (greatly increased risk)
Occurs from a mutation related to chromosome 11p13 3 which is in close proximity to WT1 gene.
Walker-Warburg syndrome (WWS), sometimes known as HARDE syndrome, is an extremely rare lethal form of congenital muscular dystrophy. It is primarily characterised by:
fetal hydrocephalus: almost always present
neuronal migrational anomalies: agyria (cobblestone lissencephaly / lissencephaly ty...
Weaver syndrome (WS) is a rare congenital disorder.
increased birth weight: fetal macrosomia
accelerated osseous maturation: increased bone age
typical facial features
Wolf-Hirschhorn syndrome (WHS) is an extremely rare chromosomal anomaly characterised by partial delection of the p arm of chromosome 4 (4p16.3).
agenesis of the corpus callosum
cleft lip + / - palat...
Wolman disease is a rare autosomal recessive inborn error of metabolism resulting in the deposition of fats in multiple organs.
Patients with Wolman disease typically present during the first two months of life with failure to thrive, diarrhoea and vomiting. Abdominal di...
Wyburn-Mason syndrome (also known as Bonnet-Dechaume-Blanc syndrome) is a rare, nonhereditary neurocutaneous disorder that typically presents with unilateral vascular malformations that primarily involve the brain, orbits and facial structures. It is currently classified as a craniofacial arteri...
Yunis Varón syndrome is a rare skeletal dysplasia. It is thought to be autosomal recessive.
severe neurologic impairment
diastasis of sutures
absent thumbs and distal phalanges of fingers
The Zuezler-Wilson syndrome (total colonic aganglionosis) is a subset of Hirschsprung disease, in which the whole colon is aganglionic. It is uncommon and accounts for 2-13% of cases of Hirschsprung disease 3. Multiple procedures have been devised to treat the condition, including proctocolectom...