≤11 ribs is associated with a number of congenital abnormalities and skeletal dysplasias, including:
Down syndrome (trisomy 21)
asphyxiating thoracic dysplasia (Jeune syndrome)
short rib polydactyly syndromes
chromosome 1q21.1 deletion...
18q-deletion syndrome is a rare chromosomal anomaly where there is a deletion of part of the long arm of chromosome 18. Associated symptoms and findings vary widely, as do their severity. Characteristic clinical features include short stature, mental retardation, hypotonia, facial and distal ske...
Aase-Smith syndrome (or Aase syndrome) is an extremely rare congenital disorder.
congenital hypoplastic anemia - fetal anemia
cleft lip or cleft palate
hydrocephalus (due to Dandy-Walker anomaly)
Abdominal migraine (AM) is a syndrome which presents as recurrent episodes of severe abdominal pain, coupled with vasomotor symptoms, nausea and emesis. Historically it has tended to be a pediatric diagnosis, but is now increasingly seen in adults. It is one of the functional gastrointestinal di...
Acrocephalosyndactyly syndromes (ACS) are a rare group of disorders collectively characterized by:
calvarial anomalies, e.g. craniosynostoses
digital anomalies, e.g. syndactyly
While there can be some overlap in features, they can be primarily classified into the following maj...
The Adams-Oliver syndrome (AOS) is a rare disorder characterized 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-Goutières syndrome is a rare hereditary neurodegenerative disease which usually presents in early infancy with systemic and central nervous system inflammatory syndrome characterized by hepatosplenomegaly, vasculopathy and encephalopathy. Many of the features are similar to congenital TO...
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).
Note: Aicardi syndrome is distinct from Aicardi-Goutieres syndrome although both are named after J...
Alagille syndrome (AGS) is a congenital genetic multi-system disorder.
Infants typically present with symptoms relating to the liver where it is one of the most common causes of hereditary cholestasis.
AGS is inherited in an autosomal fashion with a mutation of...
Alpers syndrome, also known as Alpers-Huttenlocher syndrome or progressive cerebral poliodystrophy, is a rare childhood neurodegenerative POLG-related disorder. Along with Leigh syndrome, it is one of the commonest childhood mitochondrial disorders 1.
Alpers syndrome is incredibl...
Anterior lenticonus is when the anterior surface of the lens assumes a conical shape. It can be unilateral or bilateral. Bilateral anterior lenticonus is associated with Alport syndrome.
Decreased visual activity and irregular refraction that cannot be corrected by either...
Antley-Bixler syndrome (ABS), also known as trapezoidocephaly-synostosis syndrome, is a rare autosomal dominant or recessive condition characterized by craniosynostosis and extra-cranial synostoses. Mid-facial hypoplasia is also common.
It is a very rare condition with only 50 cas...
Apert syndrome (also known as type I acrocephalosyndactyly) is a syndrome that is predominantly characterized by skull and limb malformations.
The estimated incidence is 1 case per 65-80,000 pregnancies.
increased paternal age has been proposed 6
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 be...
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 characterized by:
fetal cardiomyopathy: (dilated fetal cardiomyopathy (DCM) +/- endocardial fibroelastosis (EFE) +/- le...
Bartter syndrome is a rare inherited renal disorder.
Bartter syndrome is characterized by hyperplasia of the juxtaglomerular cells along with:
elevated plasma renin
Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder characterized by a unique set of features that can consist of:
macroglossia: most common clinical finding 4
otic dysplasia ref
localized gigantism / macrosomia
Branchio-oculo-facial syndrome (BOFS) is a very rare autosomal dominant genetic disorder that is characterized clinically by abnormalities affecting the eyes, craniofacial structures, and branchial sinuses.
More than 80 cases have been reported in the global literature since its f...
Caffey disease or infantile cortical hyperostosis is a largely self-limiting disorder which affects infants. It causes bone changes, soft-tissue swelling, and irritability.
It is distinct from physiological periostitis which can be seen involving the diaphyses of the tibiae, humeri, and femora ...
Camptodactyly arthropathy coxa vara pericarditis (CACP) syndrome is a rare condition principally characterized 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 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.
The vast m...
Cerebral hypoventilation syndrome refers to a congenital condition characterized 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 (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome comprises:
Ch: congenital hemidysplasia
I: ichthyosiform erythroderma
develops at or shortly after birth
unilateral erythema and scaling, with a distinct demarcation in the middle of the trunk 2
There are large number of recognized chromosomal anomalies (many with eponyms). When there is a change in the absolute number of chromosomes these are subgrouped as aneuploidic anomalies.
They can cause a variable degree of handicap with outcomes ranging from no effect (in some balanced translo...
Chronic hereditary lymphedema (also known as Milroy disease) is a condition characterized by lower limb lymphedema. Patients typically present with pedal edema at or before birth or soon after. Occasionally, it develops later in life.
Mutations in the FLT4 gene are thought ...
Chronic recurrent multifocal osteomyelitis (CRMO) is an idiopathic inflammatory bone disorder seen primarily in children and adolescents. It is often a diagnosis of exclusion once underlying infection and neoplasia has been ruled out. However, there are some cases in which lesion location and mo...
CLOVES syndrome is an acronym denoting a rare condition consisting of:
Congenital Lipomatous Overgrowth
Although first described as CLOVE the term "CLOVES" syndrome, with the "S" emphasizing the skeletal ...
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 contractural arachnodactyly (CCA) (also known as Beals syndrome) is a rare connective tissue disorder that bears phenotypic similarities to Marfan syndrome, but is genetically distinct. Affected individuals have arachnodactyly, muscle contractures and ear anomalies, but without any oc...
Congenital high airways obstruction syndrome (CHAOS) refers to a rare, often lethal, congenital laryngotracheal condition and is primarily characterized by obstruction to the fetal upper airway.
CHAOS can be of three possible types 2:
complete laryngeal atresia without an esophageal...
Cowden syndrome, also known as multiple hamartoma syndrome, is characterized 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 nevus, when it is considered a type of...
Crouzon syndrome is rare disorder characterized by premature craniosynostoses.
abnormal calvarial shape: in severe case can give a "cloverleaf skull"
shallow orbits with exophthalmos
mid facial hypoplasia
It carries an autosomal dominant...
Currarino-Silverman syndrome, also known as pectus carinatum type 2 deformity, is a rare disorder.
Patients present with a high carinate chest deformity due to a premature fusion of the manubriosternal joint and sternal ossification centers. Congenital heart diseases have...
The Currarino syndrome is a complex condition variably comprised of characteristic congenital anomalies of the sacrum, anorectum and presacral soft tissues. It is also known as the Currarino triad or ASP triad, however, not all three features are always present 6.
anorectal malformation or con...
Cystinosis, also known as Abderhalden Kaufmann Lignac syndrome, is the most common hereditary cause of renal Fanconi syndrome. Cystinosis is one of the lysosomal storage disorders.
It has a reported incidence of 1:192,000 1. Cystinosis is typically diagnosed in infancy.
Dorsal brainstem syndrome is a rare subset of hypoxic ischemic encephalopathy in neonates limited to the isolated involvement of the brainstem with sparing of the supratentorial brain. Due to its subtle imaging features it is often undiagnosed.
Injuries involving the tegm...
Drash syndrome, also known as the Denys-Drash syndrome, is associated with an abnormal WT1 gene (Wilms tumor gene) and consists of:
Dravet syndrome, 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.
The typical presentation occurs during the first six months to one year of life as tonic-clonic seizures in a fe...
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 characterized by osteochondromas arising from the epiphyses.
The incidence is estimated at ~1:1,000,000 3. There is a recognized 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 (trisomy 13), make up the only three trisomies to be compatible with extrauterine life in non-mosaic forms, albeit in the case of Edward syndrome only for a week or so.
The 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 high pressure and high flow 3. As su...
Familial adenomatous polyposis syndrome (FAPS) is characterized by the presence of hundreds of adenomatous polyps in the colon. It is the most common of the polyposis syndromes.
Familial polyposis coli, attenuated familial adenomatous polyposis and Gardner syndrome are all variants...
Fatco syndrome is a syndrome consisting of
tibial campomelia and
It is a syndrome of unknown genetic basis and inheritance with variable expressivity and penetrance.
Fuhrmann syndrome and Al-Awadi syndrome are said to be similar to FA...
Febrile infection-related epilepsy syndrome (FIRES) is a severe postinfectious neurological disorder that presents with status epilepticus in a previously normal child (or less commonly adult) after a febrile illness.
FIRES has received several names in the literature:
Femoral facial syndrome, also known as femoral hypoplasia-unusual facies syndrome, is a rare congenital syndrome characterized by varying degrees of femoral hypoplasia and facial dysmorphism 1.
Femoral facial syndrome can cause varying degrees of femoral malformation rang...
Fowler syndrome, also known as proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), is a rare inherited condition.
Not to be confused with Fowler syndrome of urinary retention, a condition caused by primary failure of urethral sphincter relaxation resulting ...
F. P. Weber syndrome (FPWS) is a traditional eponymous denomination of a certain type of angiodysplasia, that would nowadays rather be called a mixed hemolymphatic congenital vascular malformation (CVM) with arteriovenous (AV) shunting, based on the Hamburg classification of CVMs.
In his origin...
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
Frontonasal dysplasia, also known as median cleft face syndrome, is a rare disorder characterized by midline defects involving the face, head, and central nervous system.
Frontonasal dysplasia is considered to be a very rare condition, with approximately 100 cases having been repo...
Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by nephrotic syndrome and central nervous system (CNS) abnormalities, namely microcephaly.
Galloway-Mowat syndrome is considered extremely rare. Approximately 40 cases have been reported worldwide...
Gillespie syndrome is a rare genetic condition presenting as a mydriasis, secondary to an omnipresent partial aniridia. The abnormal iris is bilateral, with a highly-specific scalloped inner margin, due to hypoplasia of the central constrictor pupillae fibers. Associated features include an unch...
Glycogen storage disease (GSD) refers to a number of syndromes which are characterized 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 or Forbes disease
type IV: Andersen di...
Glycogen storage disease type I (GSD-I), also known as von Gierke disease, is a type of glycogen storage disease where there is excess deposition of glycogen primarily in the liver, but also in the kidney and small bowel.
It occurs approximately one in every 100,000 live births 2,...
Goldenhar syndrome (also known as oculo-auriculo-vertebral spectrum (OAVS), Goldenhar-Gorlin syndrome or facio-auriculo-vertebral dysplasia) is a complex congenital anomaly characterized 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 characterized by rhombencephalosynapsis, parietal-occipital scalp alopecia, brachycephaly, facial malformations and trigeminal anesthesia.
History and etymology
It is named after Manuel ...
The Greig cephalopolysyndactyly syndrome (GCPS) is a rare pleiotropic, multiple congenital anomaly syndrome.
It is primarily characterized by:
preaxial polydactyly (most common 2) or
mixed pre- and postaxial polydactyly
true ocular hypertelorism
A hemoglobinopathy is a genetic disorder which alters the structure of hemoglobin 1. The result is reduced oxygen-carrying capacity of the blood to the tissues, and other sequelae.
Clinical presentation varies, is related to hypoxia, and characteristically includes the fo...
Hemolytic uremic syndrome (HUS) is a multisystem thrombotic microangiopathic disease characterized by the triad of renal failure, hemolytic anemia and thrombocytopenia. It is the most common cause of renal failure in infancy and childhood requiring dialysis.
There are two forms of this syndrom...
Hemophagocytic lymphohistiocytosis (HLH), also known as macrophage activation syndrome when occurring in the setting of a rheumatologic disorder, is a non-malignant but often-fatal disorder of immune dysregulation affecting multiple organs.
It typically affects infants and young c...
Hand-foot syndrome, also known as palmar-plantar erythrodysaesthesia or Burgdorf reaction, is a benign, aseptic, self-limiting complication of many chemotherapeutic agents characterized by a widespread erythema, edema and ulceration of the hands and feet.
The Heiner syndrome is a rare form of primary pulmonary hemosiderosis associated with an allergy to cow's milk. The syndrome includes:
rectal blood loss with hypochromic microcytic anemia
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 hemihypertrophy as the cells are hyperplastic rather than hypertrophied ...
Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant monogenic COL4A1-related disorder.
The exact prevalence is unknown.
The cardinal features of HANAC syndrome are helpfully described in the name of...
Hereditary multiple exostoses, also known as diaphyseal aclasis or osteochondromatosis is an autosomal dominant condition, characterized by the development of multiple osteochondromas.
Hereditary multiple exostoses demonstrate an autosomal dominant inheritance pattern, with incomp...
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 ...
Hypoplastic left heart syndrome (HLHS) is a cyanotic congenital cardiac anomaly where affected individuals can have profound cyanosis and cardiac failure.
It is one of the commonest causes for a neonate to present with congestive cardiac failure and the 4th most frequent cardiac anomaly to mani...
Ischiopubic synchondrosis asymmetry (also known as van Neck-Odelberg disease) is characteristic enlargement of one of the ischiopubic synchondroses. It is largely considered an anatomic variant of skeletal developmental, given that it is a common and usually asymptomatic finding.
However, some ...
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...
The Jarcho-Levin syndrome (JLS) or spondylothoracic dysostosis is a rare autosomal recessive heterogeneous disorder that can occur with variable severity. Previously the condition spondylocostal dysostosis was also considered as part of the JLS spectrum but is now considered a distinct pathologi...
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 known as the oro-cranio-digital syndrome, is a rare autosomal recessive syndrome characterized by the association of the following:
cleft lip and palate
minor vertebral and rib anomalies 4
horseshoe kidneys 4
Juvenile polyposis syndrome, also referred as 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 intussuscept...
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.
Kartagener syndrome is a subset of primary ciliary dyskinesia, an autosomal recessive condition characterized by an abnormal ciliary structure 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 hemangioma thrombocytopenia syndrome, is a rare life-threatening disease found in infants in which a rapidly growing vascular tumor is responsible for thrombocytopenia, microangiopathic hemolytic anemia and consumptive coagulopathy.
Klinefelter syndrome (KS) is a sex chromosomal anomaly, which in most cases is characterized 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 te...
Klippel-Feil syndrome 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 recognized female predilection 1. Klippel-Feil syndrome has an incidence of 1:40,000-42,...
Kyphomelic dysplasias (also known as "pseudocampomelia") is thought to be a heterogeneous class of "bent bone" skeletal dysplasias. Entities included in a differential for the class are:
congenital bowing of the long bones
cartilage-hair hypoplasia (CHH; metaphyseal dysplasia, McKusick type)
Leaky lung syndrome refers to a form of non-cardiogenic pulmonary edema.
Pulmonary edema due to increased capillary permeability.
Leaky lung syndrome is considered a mild form of a part of the spectrum of acute lung injury with ARDS at the other end of the s...
Lennox-Gastaut syndrome is a form of refractory childhood-onset epilepsy and is often accompanied by developmental delay and psychological/ behavioral problems. An electroencephalogram (EEG) often shows a slow spike and wave pattern.
It often appears between the 2nd and 6th years ...
Lethal omphalocele-cleft palate syndrome is, as the name suggests, characterized 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 1.
History and etymolog...
Leukoencephalopathy with calcifications and cysts, also known as Labrune syndrome, is a rare condition that consists of a triad of leukoencephalopathy, cerebral calcifications and edematous cysts.
Leukoencephalopathy with calcifications and cysts is an extremely rare condition, wi...
Mainzer-Saldino syndrome (also known as conorenal syndrome (CRS)) is a rare condition and is one of the ciliopathies. It is due to mutations in the IFT140 gene, whose protein product is one of the six parts of the intraflagellar transport complex A.
The syndrome's key characteristics are:
Marshall-Smith syndrome (MSS) is a rare genetic syndrome primarily comprising the triad of facial dysmorphism, failure to thrive and accelerated osseous maturation 5. Many cases, however, have a wider clinical spectrum.
failure to thrive
McKusick Kaufman syndrome (MKS) is an autosomal recessive multiple malformation syndrome primarily characterized by
hydrometrocolpos - vaginal atresia
congenital heart disease
Meckel-Gruber syndrome (MGS) is classically characterized by the triad of:
renal cystic dysplasia: multiple renal cysts (present most cases)
occipital encephalocoele / holoprosencephaly (~70%)
postaxial polydactyly: usually hexadactyly (~65%)
Additional hepatic developmental defects and hepa...
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.
Megalencephaly-capillary malformation (MCAP) syndrome, also known as macrocephaly-capillary malformation syndrome, is a rare and well described genetic disorder caused by somatic mutations in the PIK3CA gene on chromosome 3q26 and characterized by early brain overgrowth and body morphogenesis an...
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-dependent mitochondrial enzymes.