A syndrome can be defined as a group of symptoms that collectively indicate or characterize a disease, psychological or congenital disorder.

The derivation is from ???-????? (Syn-drome) = running together.


ENT surgeons dealing with children need to know the ENT features of a few common syndromes for example Down syndrome, Treacher Collins syndrome and Goldenhar syndrome, as they are likely to meet children with these conditions in their paediatric practice. The ENT surgeon may be presented with two distinct clinical scenarios. Firstly, a patient with a known syndrome who presents with an ENT problem. In this instance, the ENT surgeon needs to be aware of the ENT features of the syndrome so that the appropriate investigations and management can be instigated. The second and less common situation is when the ENT surgeon suspects that a child may have a syndrome which has not yet been diagnosed. This is rightly the province of the geneticist and while it is intellectually stimulating to try to piece together a syndrome it is best to avoid mentioning any suspicions at this stage. Much anxiety can otherwise result from ready access to the internet. Nevertheless they should know how to find out about these less common syndromes. This chapter provides a brief list of the more common ENT related syndromes. Referral to a geneticist is appropriate not only for children with undiagnosed conditions but also for those with the common syndromes so that genetic counselling and genetic testing can be offered both to the immediate family and also to those in the extended family. It may be surprising how many children with known genetic diagnoses who are under multiple hospital specialties, have never seen a geneticist.

A useful book to have in the ENT department is Smith’s Recognizable Patterns of Human Malformation. The book contains pictures of children with genetic syndromes and a brief description of the main clinical features. Also Gorlin’s Hereditary Hearing Loss and its Syndromes is a useful reference source, with a particular emphasis on syndromes incorporating deafness. The London Dysmorphology Database is a computerized database, which is searchable using clinical features, and contains pictures, a brief summary of clinical features, and an abstract as well as lists of useful published papers.

Syndromes of particular relevance to the ENT Clinician

Down syndrome


Down syndrome is the most common chromosome disorder and ENT sequelae occur frequently. Most cases of Down syndrome arise from free trisomy of chromosome 21, although a small proportion are caused by translocations in which there is a high recurrence risk. The overall population incidence is between 1 in 650 and 1 in 800 live births. There is a well recognized relationship between increased risk of Trisomy 21 conceptions and maternal age. The risk of Down syndrome in women aged 35 years is 1 in 385 compared to 1 in 28 in women aged 45 years. Antenatal diagnosis is available.

ENT Features

Small ears

Narrow external ear canals: can make it difficult to view TM or insert grommet

Increased incidence of glue ear: age related

Otoacoustic emissions often non-reproducible, even in patients with normal

hearing ability

Abnormal ossicles

Mixed deafness (7%)

Sensorineural deafness (8%)

Airway obstruction from small PNS with large tonsils and adenoids


Subglottis: one anesthetic tube size smaller than expected

Unstable neck with a risk of atlanto-occipital joint subluxation in 15%, especially during general anaesthetic


General Features

Typical facial features


Upslanting palpebral fissures

Epicanthic folds Brushfield spots (speckling of iris)

Flat facial profile

Small nose with depressed nasal bridge

Mental retardation: variable IQ - can range from 20 to 85

Hypotonia: contributes to delayed motor milestones

Joint laxity

Congenital heart disease

Single palmar crease

Wide sandal gap (gap between first and second toes)

Other medical problems e.g. hypothyroidism, leukaemia

Other congenital problems e.g. duodenal atresia, Hirschsprung disease




Goldenhar Syndrome (Oculo-auriculo-vertebral spectrum/Hemifacial microsomia/First and second arch syndrome)




Unilateral or bilateral, asymmetrical congenital defects involving the first and second branchial arches are seen in Goldenhar syndrome. Involvement of other systems is common and needs to be excluded in all cases. The aetiology of the condition is unknown and most cases are a single occurrence (i.e only one family member affected) although cases with dominant and recessive inheritance are reported in the literature. Reported risk factors include maternal diabetes, bleeding in early pregnancy, twinning, high altitude (commoner in populations living at high altitude) and teratogens (thalidomide, retinoic acid derivatives). Various chromosomal abnormalities have also been reported in cases of Goldenhar syndrome.



ENT Features


Microtia: variable severity ranging from partial to complete atresia of the auditory canal and from minor degrees of microtia to complete absence of the external ear. Although the condition is usually unilateral it may occasionally be bilateral but is nearly always asymmetrical (in contrast to another common branchial arch disorder, Treacher Collins syndrome, where the features are symmetrical – see below)

Preauricular skin tags or hillocks of tissue.

Skin tags: in line between tragus and corner of the mouth

Deafness: sensorineural and/or conductive

Macrostomia: occasionally with lateral facial clefting



General Features


Facial asymmetry

Epibulbar dermoid (in which case the acronym Goldenhar syndrome is used)

Vertebral defects

Cardiac defects

Renal anomalies

Mental retardation: uncommon and chromosome analysis should be performed when this is present



Treacher Collins syndrome




Treacher Collins syndrome (TCS) is a disorder of branchial arch development and individuals have a characteristic facial appearance. It is inherited in an autosomal dominant manner and the only gene currently known to be associated is TCOF1. A high proportion of cases are caused by new mutations but significant clinical variability is common and so genetic testing may be extremely useful for recurrence risks. Classically, features are bilateral, symmetrical and congenital. There are a number of conditions in which facial features appear similar to Treacher Collins but these occur in association with limb anomalies (acrofacial dysostoses). They are caused by different genes and tend to have low recurrence risks but genetic review is important.


ENT Features


Microtia, dysplastic ears (bilateral ear anomalies)

Auricular pits/fistula/tags

Deafness: usually conductive due to external auditory canal atresia and malformations of the ossicles.

Cleft palate

Micrognathia: cleft palate and micrognanthia together may result in significant airway problems in neonates

Mandibular hypoplasia: occipitomental projection of skull and orthopantogram radiographs can assist in diagnosis

Flat malar region

Prominent nose

Broad mouth

Narrow nasopharynx

Choanal atresia (rare)


General Features


Typical facial features

Downslanting palpebral fissures

Coloboma of inferior eyelid

Sparse eyelashes



CHARGE syndrome (Coloboma – Heart defect – Atresia choanae – Retardation of growth and development – Genital defect – Ear anomalies and/or deafness)




CHARGE syndrome has a reported prevalence of 1 in 12 000. Diagnosis of CHARGE syndrome is made on the basis of clinical findings and temporal bone imaging. Mutations in the gene CHD7 can be identified in approximately 65% of cases, mostly due to new mutations. In these cases the inheritance pattern is autosomal dominant.

Patients with choanal atresia (unilateral and bilateral) need to be worked up to exclude features of CHARGE syndrome. Cardiology, ophthalmology and endocrine opinions should be sought, as well as audiology and temporal bone imaging.


ENT Features

Choanal atresia/stenosis (unilateral or bilateral)

Outer ear: short, wide ear with deficient lobe, often protruding, asymmetric

Middle ear: ossicular malformations

Temporal bone abnormalities; absent or hypoplastic semicircular canals

Sensorineural deafness (mild to profound)

General Features

Coloboma – iris, retina, choroids, disc


Cranial nerve dysfunction: anosmia, facial palsy, swallowing problems

Genital hypoplasia

Developmental delay (ranges from mild to severe; those with absent semicircular canals will have significant motor delay)

Congenital heart disease

Cleft lip/palate

Facial features: prominent forehead and nasal bridge, flat midface

Growth deficiency


22q11.2 deletion syndrome (Velocardiofacial (VCF) syndrome/DiGeorge syndrome/Shprintzen syndrome)



Microdeletion syndrome, inherited in an autosomal dominant pattern, in which the phenotype can be very variable. Features include characteristic facial features in many cases, heart defects, cleft palate, learning difficulties and immune deficiency. About 90% of probands have a de novo deletion of 22q.11.2, but the remaining 10% have inherited it from either parent. Diagnosed cytogenetically using Fluorescence in-situ Hybridisation (FISH).


ENT features


Overt, submucous or occult cleft palate

Velopharyngeal insufficiency

Nasal speech (and regurgitation of fluids)


Low set, posteriorly rotated ears

Small ears

Prominent/overfolded helices

Absent or hypoplastic ear lobules

Preauricular tags

Chronic otitis media possibly secondary to palatal problems

Sensorineural/conductive hearing loss

Narrow external auditory canals


Upper airway obstruction

Chronic sinusitis



Laryngeal web

Vascular ring



General features

Many have a characteristic facial appearance:

Prominent nasal root

Bulbous nasal tip

Hypoplastic alae nasae

Nasal dimple/bifid nasal tip

Asymmetry of face when crying

Long face


Heart: (in order of frequency of occurrence)

Teratology of fallot

Interrupted aortic archTruncus arteriosus


Vascular ring



Other important features:

Mental retardation/developmental delay (variable)

Psychiatric illness

Short stature

Feeding difficulties

Immune deficiency

Parathyroid dysfunction: hypocalcaemia




Craniosynostosis Syndromes



Crouzon, Apert, Muenke and Pfeiffer syndromes are part or the FGFR-gene related craniosynostosis syndromes. They follow an autosomal dominant inheritance pattern but new mutations are common. Saethre-Chotzen is a craniosynostosis syndrome, caused by mutations in the TWIST gene.

ENT features

Airway obstruction

Pinna abnormalities: low set, small or posteriorly rotated ears (prominent crus helices in Saethre-Chotzen).

External canal atresia

Middle ear abnormalities: both congenital ossicular fixation and eustachian tube dysfunction

Stapes fixation

Sensorineural deafness


General Features




Syndactyly – Apert syndrome

Broad, short thumbs/toes – Pfeiffer syndrome



Alport Syndrome



Condition characterised by nephropathy (proteinuria and haematuria) and sensorineural deafness. . It is caused by mutations in genes that code for collagen IV . X-linked Alport syndrome is the most common form, affecting males more severely, but autosomal recessive and dominant forms also exist and therefore it is vital that a thorough family history is obtained.


ENT Features

Hearing loss: high-tone sensorineural (mild to moderately severe) affecting 83% males and 57% females. Usually presents in school-age boys and exhibits a progressive deterioration. Adults tend to retain some hearing capacity and the impairment is more or less stable with time. Hearing aids can be of benefit.


General Features

Renal involvement:

· haematuria in childhood (males average age 3.5 years, females average age 9 years)

· proteinuria (never precedes haematuria, can develop into nephrotic syndrome)

· renal impairment (progression to end-stage renal failure in 100% of males, 15% of females)

Ocular lesions: lenticonus (most commonly anterior lenticonus) and macular flecks


Pendred syndrome

Combination of congenital deafness and thyroid dyshormonogenesis. As this often presents as non-syndromic deafness it is covered in chapter titled Non-syndromic deafness.


Usher syndrome




Usher syndrome is characterized by sensorineural hearing loss and progressive retinitis pigmentosa. It is one of the most common types of autosomal recessive syndromic hearing loss and there are three usually distinct types recognized, types 1-3, based on the degree of hearing impairment and vestibular involvement. It presents initially as non-syndromic hearing loss until the RP is diagnosed.


· Type 1


Profound congenital sensorineural deafness

Absent vestibular function (resulting in delayed motor milestones).

(Such a presentation should prompt investigation for Usher syndrome. Children should have the option of cochlear implant assessment in view of the fact that they will ultimately develop severe visual handicap in addition to their deafness.)

Retinitis pigmentosa. Asymptomatic at first (but may be diagnosed presymptomatically by ERG) but symptoms of night blindness and tunnel vision become apparent around late childhood/early puberty.



· Type 2


Congenital mild/ severe sloping sensorineural hearing loss

Normal vestibular function.

RP. Onset is around puberty (slightly later than type 1 on average)


· Type 3


Progressive hearing loss, may be postlingual onset

Normal or absent vestibular function

Retinitis pigmentosa (later and more variable age of onset)


Alstrom syndrome




Alstrom syndrome is a rare, autosomal recessive disorder caused by mutations in ALMS1 gene. It is characterised by retinal dystrophy, obesity and deafness. There is considerable clinical variability, even within sibships.


ENT Features


Progressive hearing impairment: tends to develop in second decade


General Features


Progressive retinal degeneration: no light perception by 20 years.

Visual problems can occur soon after birth and usually present within the first six months of life, presenting with photophobia and nystagmus. It is a cone-rod dystrophy in which cones are predominantly affected.

Obesity: develops during early childhood

Non-insulin dependent diabetes mellitus: develops in second/third decade

Renal complications: progressive chronic nephropathy


Other endocrine involvement



Branchio-oto-renal syndrome



Autosomal dominant disorder characterized by external, middle and inner ear anomalies, branchial sinuses and renal dysplasia. It is caused by mutations in the EYA1 gene, and less commonly in the SIX-1 gene. Extreme clinical variability can be observed in the same family.

Patients with ear pits (with or without hearing loss) and branchial defects warrant a renal ultrasound scan.


ENT Features

Ear anomalies: pits in the prehelical region and dysplastic pinnae

Conductive (due to ossicular malformations), sensorineural, or mixed hearing impairment. Inner ear malformations may include Mondini dysplasia of the cochlea, and occasionally, dilated vestibular aqueducts.

Branchial fistulae and/or cysts

Hearing impairment is not always present but the prehelical ear pits are a very highly penetrant feature.



General Features


Renal malformations: duplex collecting system, hydronephrosis, dysplasia, unilateral or bilateral renal agenesis.



Pierre Robin sequence




This condition is a disorder of embryological developmental characterized by a cleft palate and a small jaw. The primary anomaly is one of early mandibular retrognathia and this precipitates a sequence of events resulting in the features listed below.


ENT Features


Cleft palate

Retrognathia: airway obstruction, difficult intubation

Small open mouth

Myopathic facies

Prominent nose with squared-off nasal tip


Syndromes less commonly seen by ENT surgeons







Achondroplasia is the most common cause of disproportionate short stature and affected individuals have a characteristic appearance. It is an autosomal dominant disorder, caused by activating mutations in the FGFR3 gene. Incidence is related to increasing paternal age. 80% of patients have de novo mutations.


ENT Features


Obstructive sleep apnoea or central apnoea

Adenotonsillar hypertrophy

Narrow nasopharynx

Frequent otitis media and glue ear

Sensorineural and conductive hearing loss

Midface hypoplasia

Neurological involvement: cervical spine stenosis can lead to apnoea/sudden death (anaesthetic risk), spinal stenosis/nerve root compression


General Features


Disproportionate short stature

Rhizomelic (proximal) shortening of the limbs. Limitation of elbow extension

Trident configuration of the hands

Tibial bowing

Thoracolumbar kyphosis in infancy

Exaggerated lumbar lordosis, which develops when walking begins

Large head with frontal bossing

Small chest leading to respiratory compromise in infants




Beckwith-Wiedemann Syndrome



Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder caused by changes in the activity of growth promoting and suppressing genes, many of which are imprinted, found at 11p15 (including IGF2, H19, LIT1 and CDKN1C). The genetics of BWS are complex and there are different mechanisms responsible for this phenotype. 10-20% of BWS is caused by paternal uniparental disomy 11p15, causing increased expression of paternally expressed growth promoter genes (e.g. IGF2) and absence of maternally expressed growth suppressing genes (e.g. H19). 5-10% cases have mutations in CDKN1C. The recurrence risk depends on the underlying causative mechanism.


ENT Features

Macroglossia (nb. anaesthetic risk) which may occasionally require surgical reduction

Ear lobe creases and/or posterior helical ear pits
Prominent occiput
Naevus Flammeus: a strawberry mark commonly found on the forehead and eyelids

Cleft palate (rare)


General Features


Overgrowth: large birth weight, macrosomia, visceromegaly, hemi-hypertrophy. Growth rate slows around age of about 7/8 years.

Neonatal hypoglycaemia


Embryonal tumour risk increased: Wilm’s tumour, hepatoblastoma, neuroblastoma, rhabdomyosarcoma

Renal anomalies


Neurofibromatosis type 2 (NF2)




Clinically and molecularly distinct condition from Neurofibromatosis type 1. NF2 is inherited in an autosomal dominant pattern and is characterized by the presence of vestibular schwannomas. New mutations in the NF2 gene arise in approximately half of cases.


Diagnostic criteria: one of the following –

· Bilateral vestibular schwannomas

· 1st degree relative with NF2 AND

- Unilateral vestibular schwannoma


- Any 2 of: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities

· Unilateral vestibular schwannoma AND any two of: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities

· Multiple meningiomas AND

- Unilateral vestibular schwannoma


- Any 2 of: schwannoma, glioma, neurofibroma, cataract



ENT Features


Hearing loss, tinnitus or vertigo caused by Schwannoma of the cranial nerves: typically unilateral or bilateral vestibular (acoustic) neuromas. Can cause facial paralysis depending on nerve involvement.

All patients should be referred for genetic counselling as other family members may need to be monitored for the condition or tested to exclude it. Radiation therapy in NF2 patients should be considered carefully as radiation exposure, especially in childhood, can induce/accelerate tumour growth.


General Features


Other central nervous system tumours: meningiomas, ependymomas, spinal tumours, astrocytomas

Peripheral nervous system manifestations: peripheral/subcutaneous schwannomas, cutaneous neurofibromas, NF2 plaques

Café au lait patches

Ocular manifestations: cataracts, retinal hamartomas



Noonan Syndrome



Noonan syndrome is a relatively common autosomal dominant disorder and many individuals have a typical facial appearance, as well as cardiac defects and short stature. Mutations in PTPN11 have been identified in 50% of patients. 5-10% of patients with Noonan syndrome have mutations in KRAS gene. Noonan syndrome has a clinically heterogeneous phenotype, even within families.


ENT Features

Low-set, posteriorly rotated ears

Webbing of the neck, low posterior hairline

Variable hearing loss



General Features

Congenital heart disease: Pulmonary stenosis, ASD, VSD, Tetralogy of Fallot, hypertrophic cardiomyopathy

Mild mental retardation

Short stature

Sternal abnormalities

Widely spaced nipples


Epicanthal folds



Osteogenesis Imperfecta (OI)




OI is a group of inherited disorders, otherwise known as ‘brittle bone disease’. The COL1A1 and COL1A2 genes code for collagen type 1 and mutations in these genes are responsible for causing OI. Trivial trauma can result in fractures due to the skeletal fragility. The severity of the disease and deformities depends on the type of OI.

Type I is the commonest form and shows autosomal dominant inheritance. It is a relatively mild form which is non-deforming.


ENT Features (type 1 OI)

Hearing loss


General Features (type 1 OI)

Blue sclerae


Mild short stature

Wormian bones visible on skull Xray



Prader-Willi syndrome




Prader-Willi syndrome is one of the more common genetic conditions characterized by poor neonatal feeding and childhood-onset obesity as a result of hyperphagia. It is caused by the absence of the paternally derived Prader-Willi syndrome region on chromosome 15. There are several mechanisms by which this can arise for example paternal deletion, uniparental maternal disomy (two maternal copies of the critical region of chromosome 15 but no paternal copy), or abnormalities of methylation control which is the mechanism used to distinguish between maternally and paternally inherited chromosome regions


ENT Features


Obstructive sleep apnoea (OSA): secondary to obesity, a cardinal feature of the disorder.

The role of growth hormone (GH) in exacerbating OSA in Prader-Willi syndrome has been postulated following a series of fatalities of children with Prader-Willi syndrome on GH treatment. This is currently unproven but it has been suggested that GH leads to increased growth of lymphoid tissue in the airway thus worsening already existing hypoventilation or OSA.


General Features


Obesity with hyperphagia


Mental retardation

Difficult behaviour

Growth failure/short stature

Hypotonia: particularly in neonatal period


Stickler syndrome




Stickler syndrome is a hereditary arthro-ophthalmopathy. Children have a characteristic facial appearance. It is inherited in an autosomal dominant manner and the clinical phenotype can be very heterogeneous, even within families. It is a collagen disorder and the responsible mutations are found in COL2A1 and COL11A1.


ENT Features


Pierre Robin sequence

Cleft palate


Sensorineural deafness, may be progressive


Dental anomalies

Flat facies with depressed nasal bridge, anteverted nares (facial features most evident in childhood)



General Features


Severe myopia resulting from a congenital vitreous anomaly. At risk from retinal detachment.

Joint problems, especially joint hypermobility and premature arthritis



Turner syndrome



Turner syndrome is caused by partial or complete absence of an X chromosome in some (Mosaic Turner syndrome) or all cells (Classical Turner syndrome) of the body. It has a frequency of about 1 in 1800 girls.


ENT Features

Increased incidence glue ear

Sensorineural deafness

Webbed neck

Low posterior hairline


General Features

Short stature

Ovarian dysgenesis

Coarctation of aorta, bicuspid aortic valve

Renal anomalies

Mild learning difficulties

Broad chest, widely spaced nipples

Increased carrying angle

Increased incidence of autoimmune conditions: hypothyroidism, coeliac disease, inflammatory bowel disease, diabetes mellitus


Waardenburg syndrome




Waardenburg sydrome is the most common type of syndromic autosomal dominant syndromic hearing loss, characterized by hearing loss and pigmentary anomalies. There are four different types. Mutations in the PAX3 gene are responsible for types I and III. Types 1 and 3 are characterized by subtle craniofacial anomalies (below). In types 2 the appearance is normal as in type 4, which is characterized in addition by the association with Hirschprung’s disease. Mutation in the MITF gene cause some case of type II and the genes implicated in type IV include, EDNRB, EDN3 and SOX10.


ENT Features


Congenital sensorineural hearing loss

Hypoplastic nasal alae in type 1

High nasal bridge in type 1

Synophrys and medial eyebrow flare (type 1)


General Features


Pigmentary disturbances: heterochromia iridium, white forelock and eyelashes, premature greying of the hair, hypopigmentation of skin

Dystopia canthorum (lateral displacement of inner canthus of eye): type I

Limb anomalies in type 3 only.

Hirschprung’s disease in type 4 only.



Jervell and Lange-Nielsen syndrome





Homozygous form of long QT syndrome characterized by profound congenital deafness (with absent vestibular function ie. delayed motor milestones) and long QT interval on ECG. This rare condition is inherited in an autosomal recessive manner. Disease-causing mutations in the potassium channel gene KCNQ1 and its accessory subunit KCNE1, are responsible. This is an important diagnosis to make because of its high mortality if untreated.


ENT Features


Congenital profound sensorineural deafness, with absent vestibular function.


General Features


Prolonged QTc interval on 12 lead electrocardiogram

Risk of torsade des pointes ventricular tachycardia

Risk of ventricular fibrillation which can culiminate in syncope or sudden death. Can be precipitated by general anaesthesia, fright/stress, exercise (particularly swimming).



Gorlin syndrome




Gorlin syndrome is an autosomal dominant syndrome, otherwise known as naevoid basal cell carcinoma syndrome. It is caused by mutations in PTCH, a tumour suppressor gene.

ENT Features


Jaw cysts

Cleft lip and palate

Basal cell naevi/ basal cell carcinoma


General Features


Basal cell naevi/basal cell carcinoma


Frontal and biparietal bossing

Palmar/plantar pits

Ocular anomalies: cataracts, developmental defects

Calcification of falx cerebri

Rib or vertebral anomalies








Holoprosencephaly is a genetically heterogeneous disorder. Chromosomal abnormalities are responsible for the majority of cases (e.g Trisomy 13, microdeletion of 7q36). Syndromic causes, familial autosomal dominant and de novo cases have all be described. There are five known genes implicated in the pathogenesis of holoprosencephlay to date (SHH, SIX3, TG1F, ZIC2 and PTCH).


ENT Features


Oral defects: ranging from midline cleft upper lip to single central incisor/absent frenulum

Premaxillary agenesis

Midface hypoplasia

Airway obstruction

Nasal defects ranging from ‘Proboscis’ nose to single nostril


General Features


Eye anomalies ranging from cyclopia or ocular hypotelorism

Mental retardation

Other midline anomalies: congenital heart defects, anal anomalies



Larsen syndrome




Larsen syndrome is a rare skeletal dysplasia disorder. It is characterized by multiple joint dislocations and the facial phenotype. Autosomal dominant and recessive forms are reported. Mutations in FLNB (fibrilin B gene) have been found to be causative in the dominant form. Respiratory problems can occur due to upper airway compromise. Skeletal survey is required for diagnosis.


ENT Features


Tracheomalacia and laryngomalacia: lack of rigidity of tracheal and laryngeal cartilage resulting in subglottic stenosis

Flat or depressed nasal bridge

Cleft palate (uncommon)

Conductive hearing loss


General Features


Multiple joint dislocations

Short stature

Short fingers

Broad thumbs

Vertebral/spinal anomalies





Moebius syndrome




Rare condition of congenital cranial nerve palsies (predominantly affecting VIth and VIIth). Other cranial nerves can be involved and a range of other skeletal and orofacial abnormalities reported. It is usually sporadic but dominant transmission has been observed. Vascular disruption during embryogenesis has been implicated in the pathogenesis.


ENT Features


Small mouth



Variable clefting or abberant attachments of tongue: causing restricted movement and speech problems

Cleft palate


Hearing problems: glue ear

External ear malformations


General Features


Impassive face, facial asymmetry and strabismus due to congenital VI and VII palsy

Delayed motor milestones due to low muscle tone

Respiratory illnesses due to low muscle tone

Limb abnormalities ranging from aplasia to syndactyly

Mucopolysaccharidoses (MPS)



Within this group of storage disorders each type has a distinct phenotype but they share many features. Progressive connective tissue organ involvement occurs, resulting from continuous storage of dermatan sulfate in the skeleton, heart valves, spleen, liver, and cornea. Patients appear healthy at birth and have accelerated growth in the first year, followed by deceleration and short stature later in childhood.

Mucopolysaccharidoses are inherited in an autosomal recessive manner with the exception of type II (Hunter syndrome), which is X-linked. For the purposes of this chapter the different types are not described individually but awareness of the ENT complications is advised.


(The features listed below are not universal to every type of mucopolysaccharidoses)

ENT features


Obstructive airway disease and obstructive sleep apnoea.

Diffuse infiltration around airway

Hearing loss

Atlanto-axial instability in types IV and VI

Coarse or rough facial features with thick lips, enlarged mouth and tongue


General Features


Short stature

Skeletal irregularities

Viscero-megaly particularly hepatosplenomegaly

Progressive joint stiffness

Heart disease

Corneal involvement in some types

Mental retardation in some types


Teratogenic syndromes


Fetal Alcohol Syndrome





Heavy alcohol exposure in-utero can have multiple effects on the developing fetus. The resulting phenotype is variable.


ENT Features

Sensorineural hearing loss

Cleft lip +/- palate (uncommon)


General Features

Low birth weight

Growth retardation with disproportionately low weight to height relationship

Developmental delay especially impaired fine motor skills and cognition

Attention deficit disorder/behavioural difficulties

Flat malar region

Short palpebral fissues

Smooth philtrum with thin upper lip

Mild to moderate microcephaly



Fetal Cytomegalovirus syndrome


Severity of the syndrome depends on gestation at the time of intrauterine infection. Consequences of first trimester infection are relatively severe whereas third trimester infection can be asymptomatic in the fetus.




Sensorineural deafness


Learning difficulties and developmental delay




Congenital rubella syndrome


Maternal infection prior to 16 weeks gestation can result in severe consequences for the fetus.




Sensorineural deafness

Growth retardation

Mental retardation

Ophthalmic defects such as cataracts, pigmentary retinopathy

Congenital heart disease: PDA, peripheral pulmonary artery stenosis, septal defects





This chapter has covered some of the more common genetic syndromes that may be seen in the ENT clinic, with emphasis on ENT-related complications and features. With the advent of Newborn Hearing Screening, hearing loss is diagnosed early, and it is likely that the ENT surgeon may be one of the first health professionals to see a child with a syndrome. It is recommended that patients with features of a syndrome and their families are offered genetic counselling. The genetic review aims to offer a diagnostic service but in addition to this it is important that genetic testing is performed appropriately on the patient and necessary family members. It is also necessary for the family to receive counselling regarding inheritance patterns, recurrence risks and available prenatal diagnosis options. As many of the ENT-related complications will be recurrent, the ENT surgeon may well wish to find out more about the rarer syndromes of those children and adults under his or her care.




Maria Bitner-Glindzicz, Reader in Clinical and Molecular Genetics, Institute of Child Health and Great Ormond Street Hospital, London.




Figures (consent acquired in all cases when this was necessary)


1. Goldenhar’s syndrome


2. Treacher-Collins syndrome


3. Crouzon’s syndrome


4. Branchio-oto-renal syndrome (BOR), showing malformation of the pinna and a branchial sinus


5. Pierre-Robin syndrome, showing severe retrognathia, which in this case required a tracheotomy


6. Beckwith-Wiedermann syndrome, showing macroglossia


7. Cornelia de Lange syndrome


8. CHARGE syndrome


9. Waardenburg syndrome


10. Blue sclerae, in a case of osteogenesis imperfecta







Smith’s Recognizable Patterns of Human Malformation. KL Jones. W.B Saunders Company

Oxford Desk Reference Clinical Genetics. HV Firth and JA Hurst. Oxford Medical Publications

Gorlin (Head and Neck and Hereditary Hearing Loss)

LDDB (London Dysmorphology database)