Atlas of Genetic Diagnosis and Counseling || Hypoglossia-Hypodactylia Syndrome

Hypoglossia-Hypodactylia Syndrome

Hypoglossia-hypodactylia syndrome is an extremely

rare condition characterized by a small tongue associ-

ated with distal limb deficiency. The syndrome is also

called aglossia-adactylia syndrome, which is

a misnomer since the tongue is never completely

absent and the term “adactylia” does not convey the

variation in limb defects of affected individuals. The

syndrome is also known as oromandibular limb

hypogenesis syndrome, a spectrum of congenital

anomalies that affect the tongue, oromandibular

region, and the limbs.

Synonyms and Related Disorders

Aglossia-adactylia syndrome; Oromandibular limb

hypogenesis syndrome

Genetics/Basic Defects

1. Inheritance

a. Sporadic in all reported cases.

b. Autosomal dominant inheritance cannot be ruled

out.

2. Pathogenesis (Yasuda et al. 2003)

a. Impairments or insults to fetus during the early

fetal life (fourth to seventh week) may be respon-

sible for the findings of tongue and limb abnor-

malities seen in hypoglossia-hypodactylia

syndrome because of the close chronological

relationship between the development of the

tongue and the limbs.

b. A hypoplastic mandible with concurrent

hypoglossia could be explained by the fact that

the mandible originates from the same visceral

arch as the tongue.

c. Vascular mechanism (either hemorrhage or

vasoocclusion) may be responsible for defects

that are asymmetric and always distal.

Clinical Features

1. Mouth

a. Mandible

i. Micro-/retrognathia

a) Minor feeding problems in infancy

b) Minor speech impairment

ii. Oligodontia

iii. Absent mandibular incisors with concomi-

tant hypoplasia of the associated alveolar

ridge

iv. Other features

a) Mild lower lip defect

b) Microstomia (markedly reduced mouth

opening)

c) Intraoral bands

d) Oral frenula

e) Oral syngnathia

b. Tongue

i. Varying degrees of hypoglossia

ii. Ankyloglossia

iii. Marked enlargement of the sublingual mus-

cular ridges

iv. Hypertrophy of the sublingual and subman-

dibular glands

2. Variable limb anomalies

a. May involve any limb

H. Chen, Atlas of Genetic Diagnosis and Counseling, DOI 10.1007/978-1-4614-1037-9_126,# Springer Science+Business Media, LLC 2012

1113

b. Distal reduction anomalies

i. Oligodactyly (absence of some fingers and

toes)

ii. Adactylia (congenital absence of the fingers

and toes)

iii. Peromelia (severe congenital malformation

of the extremity, including absence of hand

and foot)

c. Syndactyly

3. Other associated anomalies

a. Moebius syndrome

b. Fused labia majora

c. Unilateral renal agenesis

d. Imperforate anus

4. Normal intelligence

5. Classification of syndromes of oromandibular and

limb hypogenesis (Hall 1971)

a. Type I

i. Hypoglossia

ii. Aglossia

b. Type II

i. Hypoglossia-hypodactylia

ii. Hypoglossia-hypomelia (peromelia)

iii. Hypoglossia-hypodactylomelia

c. Type III

i. Glossopalatine ankylosis

ii. With hypoglossia

iii. With hypoglossia-hypodactylia

iv. With hypoglossia-hypomelia

v. With hypoglossia-hypodactylomelia

d. Type IV

i. Intraoral bands and fusion

ii. With hypoglossia

iii. With hypoglossia-hypodactylia

iv. With hypoglossia-hypomelia

v. With hypoglossia-hypodactylomelia

e. Type V

i. The Hanhart syndrome

ii. Charlie M syndrome

iii. Pierre Robin syndrome

iv. Moebius syndrome

v. Amniotic band syndrome

6. Differential diagnosis with other oromandibular

limb hypogenesis syndromes (Bonneau et al. 1999)

a. Hanhart syndrome

i. Micrognathia

a) Microglossia

b) Hypodontia

ii. Limb anomalies

a) Ranging from stunted digits, oligodactyly,

to more severe peromelia

b) May affect any limb

b. Glossopalatine and ankylosis syndrome

i. Tongue.

a) Usually attached to the hard palate

b) May adhere to the maxillary alveolar

ridge

c) Mildly cleft tongue tip

ii. High-arched or cleft palate.

iii. Hypoplastic mandible.

iv. Hypodontia principally affects the incisor

teeth.

v. Ankylosis of the temporomandibular joint.

vi. Facial paralysis.

vii. Extremely variable limb anomalies.

a) Oligodactyly

b) Syndactyly

c) Polydactyly

d) Peromelia

c. Limb deficiency-splenogonadal fusion syn-

drome (Bonneau et al. 1999)

i. Splenogonadal fusion

a) A rare malformation in which the spleen is

abnormally connected to the gonad, or,

more rarely, to a derivative of the

mesonephros

b) May occur as a rare malformation

ii. Association with other malformations, espe-

cially with terminal limb defects

d. Moebius syndrome (please refer to the chapter of

Moebius Syndrome)

Diagnostic Investigations

1. Radiography

a. Fusion of the temporomandibular joints

b. Micro-/retrognathia

c. Hypodontia

d. Limb defects

i. Variable distal limb deficiency

ii. Asymmetric reduction deformities of the

distal extremities

iii. Severity ranging from hypoplastic digits to

peromelia

1114 Hypoglossia-Hypodactylia Syndrome

e. Other rare anomalies

i. Dextrocardia

ii. Transposition of abdominal organs

iii. Jejunal atresia

iv. Short bowel

v. “Apple peel” bowel

2. Reconstructed 3D CT imaging of the craniofacial

skeletal structures (Yasuda et al. 2003)

a. Retruded and reduced mandible

b. Steep inclination of the anterior surface of the

mandible in relation to the lower mandibular

plane

c. Bone defect of the alveolar ridge at the midline

area of the mandible

3. MRI of the tongue and the floor of the mouth

(Yasuda et al. 2003)

a. Degree of the hypoglossia

b. Space between the tongue and the inferior sur-

face of the palate

c. Hypertrophy of the floor of the mouth

Genetic Counseling

1. Recurrence risk

a. Patient’s sib: not increased

b. Patient’s offspring: not increased unless the con-

dition represents an autosomal dominant inheri-

tance, in which case there will be 50% risk to

have an affected offspring

2. Prenatal diagnosis: not been reported

3. Management (Yasuda et al. 2003)

a. Early surgical intervention for presence of severe

anomalies that are life-threatening and interfere

swallowing, breathing, and eating

b. Extraction of the supernumerary tooth

c. Orthodontic expansion appliance for widening

the mandibular dental arch

d. Distraction osteogenesis to improve the size and

shape of the hypoplastic mandible

e. Mandibular advancement

References

Alexander, R., Friedman, J. S., Eichen, M. M., et al. (1992).

Oromandibular-limb hypogenesis syndrome: Type II A,

hypoglossia-hypodactylia–report of a case. The British Jour-nal of Oral & Maxillofacial Surgery, 30, 404–406.

Alvarez, G. E. (1976). The aglossia-adactylia syndrome. BritishJournal of Plastic Surgery, 29, 175–178.

Bersu, E. T., Pettersen, J. C., Charboneau, W. J., et al.

(1976). Studies of malformation syndromes of man

XXXXIA: Anatomical studies in the Hanhart syndrome–a

pathogenetic hypothesis. European Journal of Pediatrics,122, 1–17.

Bonneau, D., Roume, J., Gonzalez, M., et al.

(1999). Splenogonadal fusion limb defect syndrome: Report

of five new cases and review. American Journal of MedicalGenetics, 86, 347–358.

Cohen, M. M., Jr., Pantke, H., & Siris, E. (1971). Nosologic and

genetic considerations in the aglossy-adactyly syndrome.

Birth Defects Original Article Series, 7(7), 237–240.Coskunfirat, O. K., Velidedeoglu, H. V., Demir, Z., et al. (1999).

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Annals of Plastic Surgery, 42, 333–336.David, A., Roze, J. C., Remond, S., et al. (1992). Hypoglossia-

hypodactylia syndrome with jejunal atresia in an infant of

a diabetic mother. American Journal of Medical Genetics,43, 882–884.

Dellagrammaticas, H., Tzaki, M., Kapiki, A., et al. (1982).

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itance. Progress in Clinical and Biological Research, 104,299–305.

Elalaoui, S. C., Ratbi, I., Malih, M., et al. (2010). Severe form of

hypoglossia–hypodactylia syndrome associated with com-

plex cardiopathy: A case report. International Journal ofPediatric Otorhinolaryngol, 74(9), 1092–1094.

Gorlin, R. J., Cohen, M. M., Jr., & Hennekam, R. C. M. (2001).

Syndromes of the head and neck (4th ed.). New York: Oxford

University Press.

Grippaudo, F. R., & Kennedy, D. C. (1998). Oromandibular-

limb hypogenesis syndromes: A case of aglossia with an

intraoral band. British Journal of Plastic Surgery, 51,480–483.

Hall, B. D. (1971). Aglossia-adactylia. Birth Defects OriginalArticle Series, 7(7), 233–236.

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Aglossia-adactylia syndrome. American Journal of Diseasesof Children, 119, 255–256.

Herrmann, J., Pallister, P. D., Gilbert, E. F., et al. (1976). Studies

of malformation syndromes of man XXXXI B: Nosologic

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a b

c

Fig. 1 (a–c) A 2-month-old

female infant with

hypoglossia-hypodactylia

syndrome showing

antimongoloid slant of the

palpebral fissures, facial palsy,

micro-/retrognathia,

microstomia, hypoglossia, and

limb anomalies with adactylia

of the right hand and both feet

and oligodactyly of the left

hand


a b

Fig. 2 (a, b) Another infant with hypoglossia-hypodactylia syndrome showing extreme micro-/retrognathia, hypoglossia,

microstomia, and adactylia of both hands


a b

c

Fig. 3 (a–c) A 3-month-old

girl with hypoglossia-

hypodactylia syndrome

showing extreme micro-/

retrognathia, hypoglossia,

microstomia, and adactylia of

both hands (right upperextremity showed a transverse

growth arrest beyond the wrist

and left upper extremity

showed a transverse arrest

beyond the proximal one third

of the forearm)


a bFig. 4 (a, b) CT of the face

(AP and lateral views) show

left hemimandibular agenesis

(complete absence of the

body, angle, ramus, and

condyle) and a significant

aplasia of posterior maxilla on

the left

a bFig. 5 (a, b) Plainradiographs show transverse

growth arrest past the

proximal one third of the left

forearm and V-shaped

formation of the radius and

ulna with growth arrest past

the right wrist


Fig. 6 The previous girl was seen at 3 years of age

a

b

Fig. 7 (a, b) Preoperative photos at 5 years of age


Fig. 8 Preoperative CT at the age of 5

Fig. 9 Intraoperative photo. Costochondral graft fixated to the

adjacent mandible. Cartilaginous cap seated in the glenoid fossa

Fig. 10 Titanium mesh used as a crib for BMP at the inferior

border of the rib graft


a b

Fig. 11 (a, b) Postoperative photos at age 5. She was

reconstructed with a right costochondral rib graft to replace the

condyle and ramus region and established continuity of her

mandible. This was combined with the use of a titanium mesh

crib and some bone morphogenetic proteins (BMP) at the

junction of the native mandible and the costochondral graft.

Note the improved facial profile on the left. Despite improved

result, the patient will require further surgery as she grows to

correct her facial profile

Fig. 12 Three-month postoperative cone beam CT. Cartilagi-

nous cap not apparent on this view

Fig. 13 Note the broad intraoral band extending from the left

subglossal region to the soft palate. This band also attaches to the

left lower lip causing retraction of the lip


Fig. 14 The patient protruding her tongue past the intraoral

band. Maximum protrusion. Based on the hypoglossia, the oral

band extending from the floor of mouth and left cheek to the soft

palate, and the limb abnormalities (hypodactylomelia), the

patient would fit best as Hall’s type IVD (intraoral bands and

fusion with hypoglossia-hypodactylomelia. Thus, the patient is

classified as a type IVD with hemimandibular agenesis (Qaisi

et al. 2010)


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Atlas of Genetic Diagnosis and Counseling || Hypoglossia-Hypodactylia Syndrome