A. Incidence and etiology.

1. Most common autosomal chromosomal abnormality in live-born infants; occurring in 1 in 800 infants (Haldeman-Englert et al., 2012b).

2. Full trisomy 21 occurs in 94% of cases (all or large part of the chromosome). Affected individuals have 47 chromosomes (three of chromosome 21) (Fig. 35-2).

3. Greater than 90% of trisomy 21 cases result secondary to meiotic disjunction. Maternal age exerts a significant effect. Three percent to 5% of cases are de novo or caused by a balanced translocation that becomes unbalanced (Haldeman-Englert et al., 2012b).

4. Mosaic or mitotic nondisjunction Down syndrome, presenting with variable phenotypic expression, is demonstrated in 3% of affected infants (Haldeman-Englert et al., 2012b).

5. Greater than 50% of trisomy 21 fetuses abort early in pregnancy.

6. Recurrence risk approximately 1% overall. For those parents who are known translocation carriers, the risk is substantially higher. Risk for carrier parent is dependent on the type of translocation and the sex of the parent (Jones et al., 2013).

7. Incidence of Down syndrome related to maternal age is as follows (Moore and Persaud, 2013):

a. 20 to 24 years—1 in 1400.

1. Craniofacial.

a. Brachycephaly with flattened occiput, presence of third fontanelle.

f. Prominent, protruding tongue; high-arched palate with tendency to keep mouth open (Jones et al., 2013).

2. Musculoskeletal.

a. Hypotonia: generalized—poor Moro reflex present in 80% of infants. Suck may be weak.

e. Wide spacing between first and second toes (Matthews and Robin, 2011).

3. Skin.

a. Short neck with excess nuchal skin.

1. Prematurity.

2. Mental retardation: present in all cases, variable degree, mild to moderate impairment (Lashley, 2005).

3. Hematologic: bone marrow dyscrasias, including neonatal thrombocytopenia and transient self-resolving myeloproliferative disorders, have been described within the first year of life (Haldeman-Englert et al., 2012b). Thirty percent of infants with Down syndrome and transient myeloproliferative disease develop acute megakaryoblastic leukemia within the first 4 years of life (Luchtman-Jones et al., 2011).

4. Gastrointestinal: duodenal atresia/stenosis—occur in 2% to 5% of cases; esophageal atresia, imperforate anus, fistulas, webs.

5. Cardiac anomalies in approximately 50% of infants: endocardial cushion defect, ventral septal defect, patent ductus arteriosus, atrial septal defect, tetralogy of Fallot (Haldeman-Englert et al., 2012b).

6. Otitis media, hearing impairment.

D. Diagnosis.

1. Chorionic villus sampling at 9 to 12 weeks of gestation.

5. Standard chromosome banding techniques provide confirmation of trisomy 21 and differentiate those infants having nondisjunctional trisomy from a translocation. In those infants with confirmed translocation, each parent should have karyotype analysis done to rule out carrier status as recurrence risk is significantly increased (Lewanda et al., 2006).

6. FISH: region on chromosome affected is q22.2.

E. Treatment.

1. Initial treatment geared to expressed symptoms.

3. Ophthalmologic evaluation should be undertaken as children with Down syndrome have greater incidence of cataracts, strabismus, myopia, and glaucoma (Haldeman-Englert et al., 2012b).

4. Monitor cerebral spine for spinal cord compression.

5. Monitor growth as velocity often decreases—weight and head circumference.

6. Screen for hypothyroidism.

7. Upper respiratory infections and ear infections are common.

8. Cardiac sequelae, including congestive heart failure.

9. Aimed at optimizing potential for intellectual and social growth.

10. Developmental delays—muscle tone increases with age, rate of developmental progress slows with age (Jones et al., 2013). Early developmental enrichment programs seem to be of the most value.

11. Social performance is usually above the expected level. Emotional problems are apparent in many affected individuals. Parents must be provided with resources for emotional and medical support.

12. Following correction of associated congenital malformations, less than 50% of individuals with Down syndrome survive to age 60. Less than 15% survive to age 68 (Haldeman-Englert et al., 2012b).

Trisomy 18

A. Incidence and etiology.

1. Affected infants have 47 chromosomes (three of chromosome 18) (Fig. 35-3).

2. Occurs in 1 in 600 births; females more often than males (3:1) (Jones et al., 2013). Trisomy 18 is the third most common autosomal disorder. Associated with a high rate of intrauterine demise—5% of affected cases will survive to birth (Haldeman-Englert et al., 2012b).

3. Eighty percent of cases are caused by chromosomal nondisjunction (Lewanda et al., 2006); 95% of infants have three copies of entire chromosome 18, and 5% have either partial trisomy or mosaicism of most of the long arm of 18 (Haldeman-Englert et al., 2012b).

4. Occurs more frequently as maternal age advances: mean maternal age is 32 (Jones et al., 2013).

5. Three patterns of presentation have been described:

a. Severe: most body cells display abnormality. Handicaps are severe, with a short life expectancy.

c. Partial: dependent on the portion of the chromosome affected. Infants with trisomy of the short arm of the chromosome have minimal handicaps and few abnormalities are expressed. Infants with trisomy involving the entire long arm of the chromosome display the full spectrum of the syndrome. Infants with trisomy of the distal one third of the chromosome demonstrate a partial syndrome with less profound mental deficit and longer survival (Jones et al., 2013).

6. Estimate for risk of recurrence for future pregnancies is 1% over the maternal age-specific risk for any viable autosomal trisomy (Haldeman-Englert et al., 2012b). Infants whose defect is secondary to a structural arrangement warrant parental karyotype analysis.

B. Clinical presentation.

1. General: growth deficiency, hypoplasia of skeletal muscle, subcutaneous and adipose tissue (Haldeman-Englert et al., 2012b).

2. Craniofacial: small narrow cranium, prominent occiput, low-set malformed auricles, atresia of auditory canals, narrow palpebral fissures, microphthalmia, corneal opacities, colobomas, micrognathia, microstomia and high-arched palate, cleft palate (Lewanda et al., 2006).

3. Musculoskeletal: clenched hand, with index finger overlapping the third finger and the fifth finger overlapping the fourth, abnormal creases, low-arch dermal ridge pattern on six or more fingertips, hypoplasia of nails, short sternum, narrow pelvis with hip dislocation, rocker-bottom appearance to feet, hammer toes, clubfeet, and syndactyly between toes 2 and 3 (Jones et al., 2013).

4. Skin: redundant skin, mild hirsutism of back and forehead.

C. Associated findings.

1. Cardiac anomalies: varied. Occur in 95% of cases (Lashley, 2005). Ventricular septal defects and patent ductus arteriosus, atrial septal defects, pulmonic stenosis, coarctation of the aorta are most common (Haldeman-Englert et al., 2012b).

2. Renal anomalies: horseshoe kidneys, ectopic kidneys, double ureters, and cystic kidneys.

3. Genital abnormalities: cryptorchidism in males. Hypoplasia of labia and prominent clitoris in females.

4. Umbilical hernias.

5. Severe psychomotor retardation.

D. Diagnosis.

1. Chorionic villus sampling at 9 to 12 weeks of gestation.

3. Maternal serum triple screening revealing low levels of AFP, unconjugated estradiol, and total human chorionic gonadotropin. Fifty percent to 60% of trisomy 18 cases can be detected with second-trimester screening utilizing the triple screen (Blackburn, 2013).

4. Ultrasound targeting growth retardation, oligohydramnios and polyhydramnios, heart defects, myelomeningocele, and limb abnormalities.

5. Following delivery, standard chromosome banding assay or FISH.

E. Treatment.

1. Infants with full trisomy 18 are usually fragile, with a history of feeble fetal activity (Jones et al., 2013). Prognosis for infants with this disorder is poor. More than 90% of infants will succumb in the first 6 months of life, 5% will survive to 1 year (Haldeman-Englert et al., 2012b).

2. Children who survive the first year of life deal with feeding issues secondary to hypotonia, growth issues, and significant developmental disability. These children generally do not walk unsupported or develop expressive language, but can be capable of limited verbal communication and some social interaction.

3. Once a diagnosis has been confirmed, decisions about extraordinary medical means for prolongation of life present nearly overwhelming challenges for families. Individual circumstances for each family must be considered (Jones et al., 2013). Most deaths result secondary to congestive heart disease, infection, and central apnea (Haldeman-Englert et al., 2012b).

4. For those infants surviving the immediate newborn period, care is supportive and individualized to the infant’s needs.

5. Parents should be offered genetic counseling and provided with resources for support.

Trisomy 13

A. Incidence and etiology.

1. Affected infants are born with 47 chromosomes instead of the usual 46, with the extra genetic material located on chromosome 13. This abnormality is the rarest of the trisomies, severe external malformations are common, and only 2% to 3% survive to term (Lashley, 2005).

2. Defect occurs in 1 in 12,500 to 1 in 21,000 live births (Haldeman-Englert et al., 2012b), making it the fourth most common autosomal dominant disorder.

a. Older mothers are more likely to have an infant with this aneuploidy defect.

b. Slightly more boys than girls are affected (Jones et al., 2013).

3. Seventy-five percent of cases result from chromosomal nondisjunction (Lewanda et al., 2006).

4. The etiology for this disorder is trisomy of all or part of chromosome 13.

a. Eighty percent of affected infants have three complete copies of chromosome 13.

(1) Survival for infants with mosaicism is usually longer.

(2) Degree of mental deficit is variable (Jones et al., 2013).

c. Partial trisomy of the proximal segment is characterized by infants with severe mental deficiency and an overall pattern of full trisomy 13.

d. Partial trisomy of the distal segment results in severe mental deficiency and characteristic phenotype (Jones et al., 2013).

B. Clinical presentation.

1. General: growth deficiency.

2. Craniofacial: cebocephaly, microcephaly, microphthalmia, colobomata, glaucoma, midline scalp defects, retinal dysplasia, cleft lip and/or palate (60% to 80%) (Jones et al., 2013), malformed ears, atresia of external auditory canals, deafness, prominent nasal bridge, short neck with excessive skin.

a. Aplasia cutis congenita is a congenital localized absence of skin often involving the scalp along the midline. Lesions have sharp margins and may present as ulcers, bullae, or scars (Tran and Cohen, 2012). Lesions are frequently noted on the scalp near the parietal hair whorl (Graham, 2007). Most defects are small and superficial; 20% involve absence of the skull, exposing the infant to hemorrhage and infection.

3. Musculoskeletal: polydactyly, single palmar crease, overlapping of fingers, flexion deformities of hands and wrists, prominent heel resulting in rocker-bottom feet, thin posterior ribs with or without missing rib, and hypoplasia of pelvis with shallow acetabular angle.

4. Genital abnormalities: males—cryptorchidism, abnormal scrotum; females—bicornuate uterus.

5. Central nervous system (CNS): holoprosencephaly found in 50% of patients with incomplete development of the forebrain and olfactory and auditory nerves, seizure activity, apnea in early infancy, and severe mental deficiency (Haldeman-Englert et al., 2012b).

6. Capillary hemangiomas, localized scalp defects—cutis aplasia.

C. Associated findings.

1. Cardiac anomalies occur in approximately 80% of infants: ventral septal defects, dextrocardia, patent ductus arteriosus, atrial septal defects.

1. Chorionic villus sampling between 9 and 12 weeks of pregnancy.

1. The presence of holoprosencephaly is the single most important finding predicting survival.

2. Prognosis is extremely poor—80% mortality in the newborn period has been documented (Haldeman-Englert et al., 2012b). Survivors frequently have seizures, severe mental retardation, and failure to thrive.

3. Feeding issues are related to the smallness of the lower jaw and poor muscle tone.

4. For those infants with cleft lip and/or palate, feeding issues present additional challenges.

5. The high rate of early mortality for this syndrome requires the parents to prepare for the infant’s death as well as plan for supportive care. The desires of the parents must be taken into account as care is designed for each patient.

22q11.2 Deletion Syndrome

This syndrome has been referred to as DiGeorge syndrome, Sprintzen syndrome, or velocardiofacial syndrome. It is the most commonly occurring microdeletion syndrome in humans (Haldeman-Englert et al., 2012b).

A. Incidence and etiology.

1. Occurs in 1 in 3000 infants (Haldeman-Englert et al., 2012b). This syndrome is extremely variable in expression and varies from patient to patient.

2. Inherited as an autosomal dominant pattern.

3. Individuals have an interstitial deletion of 22q11.2; 80% to 90% of patients have the same large deletion (Haldeman-Englert et al., 2012b).

4. Most 22q11 deletions occur as de novo lesions—less than 10% are inherited from an affected parent. Both parents must be tested to determine carrier status (Jones et al., 2013).

B. Clinical presentation.

1. Growth: postnatal onset of short stature (Jones et al., 2013).

2. Craniofacial: microcephaly, velopharyngeal insufficiency, palatal anomalies, small or absent adenoids, prominent nose with bulbous tip, narrow palpebral fissures, long face, retruded mandible with chin deficiency, small mouth—associated with swallowing abnormalities, hooded eyelids, hypertelorism, hearing deficits, and minor auricular abnormalities.

3. Musculoskeletal: limbs are slender, hypotonic; hands and fingers are hyperextensible (Jones et al., 2013).

C. Associated findings.

1. Cardiac defects are present and usually significant in 85% of patients. Most common defects include ventral septal defects, right interrupted aortic arch, tetralogy of Fallot, and truncus arteriosus (Jones et al., 2013).

2. Atresia or hypoplasia of the thymus and parathyroid glands (Haldeman-Englert et al., 2012b).

3. Functional T-cell abnormalities.

4. Hypocalcemia: occurs as a transient finding in neonates (60%). Seizures can occur—usually as a result of hypocalcemia.

5. Learning disabilities: 62% of patients will have normal or mild learning issues, with severe or moderate learning difficulties in 18% (Jones et al., 2013). Developmental delays in language and speech are common (Haldeman-Englert et al., 2012b).

6. IQ range variable. One third of patients function within normal range.

7. Psychiatric disorders—schizophrenia.

8. Speech and language are often delayed. Speech pattern is frequently nasal secondary to poor pharyngeal musculature.

D. Diagnosis.

1. Defect is detected by FISH.

1. Death primarily secondary to cardiac defects—occurs in approximately 8% of infants (Jones et al., 2013).

2. Hypotonia is common, resulting in developmental delays. Early intervention, physical and speech therapy are helpful, especially with feeding issues.

3. Infants may require surgical intervention for palatal abnormalities to improve speech.

4. Infants frequently demonstrate greater socialization skills than intellectual skills.

5. Onset of psychiatric symptoms is usually between 10 and 21 years of age—schizophrenia and depression are the most common conditions. Ongoing assessment and support are essential (Jones et al., 2013).

A. Incidence and etiology.

1. Affected individuals have monosomy—loss of all or part of one copy of the X chromosome in a female. Most 45,X conceptuses die early—0.1% survive to term, the majority are spontaneously aborted (Haldeman-Englert et al., 2012b).

a. Loss of the entire chromosome occurs in approximately 50% of cases (Lewanda et al., 2006).

2. Occurs in approximately 1 in 2500 live-born phenotypic females (Haldeman-Englert et al., 2012b).

3. In 70% to 80%, the paternal X chromosome is missing (Lashley, 2005).

4. Mosaicism is associated with complex karyotypes, ring chromosomes, and deletions.

5. Disorder generally occurs as a sporadic event in a family (Jones et al., 2013).

B. Clinical presentation.

1. Growth: short stature.

3. Musculoskeletal: broad chest with wide-spaced nipples, pectus excavatum, short fourth metacarpal/metatarsal, marked lymphedema of extremities, bone dysplasia, dislocation of the hip, knee abnormalities (Lewanda et al., 2006).

4. Skin: excessively pigmented nevi, loose skin—especially posterior folds of neck.

5. Lymphatic: Impaired lymph drainage leads to distention of lymphatics, and peripheral lymphedema, particularly of dorsa of hands and feet (Kalhan and Devaskar, 2011).

C. Associated anomalies.

1. Cardiac defects: bicuspid aortic valve, coarctation of aorta, valvular aortic stenosis, and mitral valve prolapse (Haldeman-Englert et al., 2012b).

2. Renal: horseshoe kidney, unilateral renal agenesis.

3. Gonads: ovarian dysgenesis with hypoplasia owing to lack of germinal elements (Jones et al., 2013).

4. Performance issues: delayed motor skills, poor coordination, clumsiness, problems with nonverbal problem solving, depression and poor self-esteem in young adults (Jones et al., 2013).

D. Diagnosis.

1. Ultrasound for short stature, monitoring of growth throughout gestation.

1. Growth issues persist throughout childhood and adolescence. Growth is commonly normal within the first 3 years of life, decreasing during school-age years, more dramatically during teenage years when these girls do not get their usual growth spurt at puberty. Growth hormone therapy is generally begun at around 4 to 5 years of age. Significant improvement in final height has been achieved (Haldeman-Englert et al., 2012b).

2. Congenital lymphedema requires symptomatic treatment initially, presenting with edema of hands and feet secondary to faulty lymph drainage.

3. Ovarian function is affected, with primary ovarian failure occurring secondary to gonadal dysplasia. The result can be delay in development of secondary sex characteristics and primary amenorrhea. Treatment options include cyclic estrogen replacement therapy for hypogonadotropic girls beginning at ages 13 to 14 (Haldeman-Englert et al., 2012b).

4. Ongoing evaluation of congenital heart defects is necessary secondary to the increased risk for dissection of the aorta. Coarctation of aorta must be surgically repaired.

5. With increasing age, greater incidences of osteoporosis, autoimmune thyroid disease, and chronic liver disease have been reported (Jones et al., 2013). Close monitoring for these conditions is needed.

6. For those infants for whom their physical appearance would be aided by plastic surgery, concerns for the formation of keloid scars must be considered.

7. School performance may be affected primarily in word comprehension, perceptual thinking, and presentation (Haldeman-Englert et al., 2012b). Intelligence is usually normal.

Klinefelter’s Syndrome

A. Incidence and etiology.

1. Affects approximately 1 in 1000 males, making it the most common single cause of hypogonadism and infertility in males (Moore and Persaud, 2013).

2. Chromosomal analysis reveals a 47,XXY karyotype.

a. Parental nondisjunction errors account for one half of the affected infants; maternal meiosis errors accounting for the majority of remaining cases (Lewanda et al., 2006).

b. Advanced maternal age is related to an increased incidence for those whose defect is secondary to maternal factors.

c. According to Jones et al. (2013), older fathers are at higher risk for producing a higher number of XY sperm, resulting in a higher risk of having an infant with Klinefelter’s syndrome.

3. Infants with XXY/XY mosaicism may have a greater potential for testicular function.

4. Infants carrying XXYY karyotype are more often developmentally delayed.

B. Clinical presentation.

1. General: affected males frequently have long limbs, reduced upper- to lower-segment ratio (Moore and Persaud, 2013). Tall and slim stature.

2. Musculoskeletal: elbow dysplasia, fifth finger clinodactyly.

3. Genital: hypogonadism, cryptorchidism, hypospadias, gynecomastia.

C. Associated findings.

1. Cancers: teratoma, leukemia, breast most common.

2. Scoliosis during adolescent years (Jones et al., 2013).

3. School performance and behavioral issues: delayed speech and language development, difficulties with auditory processing and auditory memory. Aggressive behavior is observed (Moore and Persaud, 2013).

D. Diagnosis.

1. Prepubertal males have no significant dysmorphism. Condition may not be diagnoses until puberty, with incomplete development of secondary sex characteristics and infertility (Lashley, 2005). Minor abnormalities are helpful in providing clues for diagnosis: penile size, skeletal defects (Lewanda et al., 2006).

2. Chromosomal testing, FISH to determine XXY or XXYY or XXXY status.

E. Treatment.

1. As adolescence progresses, screening for scoliosis is needed.

2. Deficient testosterone and elevated gonadotropin levels signal the need for hormone replacement. Boys must be monitored for prospective testosterone replacement as they near ages 10 to 12. As some males have incomplete or inadequate puberty, replacement will assist in development of a more masculine physique, increase pubic and facial hair, and improve bone density and muscle mass (Jones et al., 2013). Delays in treatment can increase risk for osteoporosis.

3. The incidence of breast cancer for affected infants is 20 times higher than the general population, but only 1 in 5000 affected men. Routine mammography is not required (Jones et al., 2013). Incidence of mediastinal teratomas is 34 to 40 times that of nonaffected populations. Ongoing assessment of these individuals is needed.

4. IQ range for affected individuals is variable, from well below to well above average. Assistance in school is commonly required, especially in the areas of reading and spelling.

5. Emotional and behavioral problems persist and may increase throughout childhood. Formation of peer relationships may be difficult secondary to insecurity, shyness, and poor judgment activity. Support with psychological adjustment is needed.

Osteogenesis Imperfecta

A. Incidence and etiology.

1. Disorder is caused by mutations of COL1A1 and COL1A2 genes on chromosomes 17q21 and 17q22.1. The result of the mutation is an abnormality of type I collagen (Rimoin and Tiller, 2012). Overall incidence is 3 to 4 per 100,000.

2. Six clinical types are identified:

a. Type I: autosomal dominant, resulting from mutations of COL1A1 gene on chromosome 17q21 (Jones et al., 2013). Most common form found in most populations. Characterized by bone fragility with onset of fractures following birth.

b. Type II: autosomal dominant, inheritance pattern occurring secondary to a sporadic, dominant mutation in one of the two collagen genes (Jones et al., 2013).

(1) Frequency 1 in 20,000 to 60,000 (Rimoin and Tiller, 2012). Lethal in the perinatal period—either as stillborn or secondary to respiratory failure; 80% die within the first month of life. Recurrence risk is described as 6%.

c. Type III: primarily an autosomal dominant inheritance pattern, although rare autosomal recessive pattern has been identified (Jones et al., 2013). Progressive and deforming; if not present at birth, fractures and deformations develop in first and second years of life (Rimoin and Tiller, 2012).

d. Type IV: autosomal dominant pattern resulting from mutations of the two collagen genes. Significant bone deformities are common.

e. Type V: autosomal dominant inheritance pattern that is not associated with collagen type I mutations (Jones et al., 2013). Moderate tendencies to fracture long bones.

f. Type VI: pattern of inheritance is unknown. Results from a mineralization defect; fractures occurring later between 4 and 18 months.

B. Clinical presentation.

1. Type I.

a. Growth: near-normal or normal growth pattern.

b. Craniofacial: macrocephaly, triangular appearing facies, hearing impairment, altered dentition with hypoplasia of dentin and pulp (Jones et al., 2013).

c. Musculoskeletal: postnatal onset of mild limb problems; bowing of femur, tibia, scoliosis, hyperextensibility of joints, and osteopenia.

d. Skin: translucent, easy bruising, blue sclerae secondary to partial visualization of the choroid.

2. Type II.

a. Growth: short-limbed growth deficiency with prenatal onset, low birth weight.

b. Craniofacial: head is soft and boggy, with minimal calvarial bone palpable, large fontanelles, deep blue sclerae, shallow orbits; head assumes a triangular shape (Rimoin and Tiller, 2012).

c. Musculoskeletal: shortened and bowed limbs with extra skin, flexed and abducted hips, flattened vertebrae (Jones et al., 2013).

3. Type III.

a. Growth: prenatal onset of growth deficiency, extremely short stature.

c. Musculoskeletal: kyphoscoliosis, which may lead to respiratory distress (Jones et al., 2013), multiple fractures, and deformations of limbs at birth.

4. Types IV to VI.

a. Presentation less severe for these forms. Stature and growth may be mildly affected; fractures, if they occur, present later. Sclerae may be mildly affected or absent. Dentition is less commonly affected.

1. Conductive hearing loss secondary to deformity of the small bones of the ear.

3. Corneal clouding and keratoconus, megalocornea (Jones et al., 2013).

4. Cardiac: floppy mitral valve.

5. Scoliosis developing later, progressing during puberty, sometimes resulting in severe deformity in adulthood. Loss of height may occur secondary to progressive spinal osteoporosis in adults.

D. Diagnosis.

1. Prenatal diagnosis is possible with ultrasonography and mutation analysis.

a. Type I: femurs are short, broad, or crumpled. Fibulas may be thin.

1. Depending on the type of osteogenesis, treatment will vary extensively. Type I patients may require little or no treatment, whereas type II patients may die before any treatment is begun. Types III and IV are the most complex, requiring intensive support. Treatment is centered around minimizing pain and prevention of future fractures.

a. Initial treatment of fractures is aimed toward alignment of bones to avoid deformity, comfort measures, prevention of further deformity, optimizing function following healing, and prevention of further fractures.

d. Administration of bisphosphonates to increase bone density and decrease fracture has been suggested (Rimoin and Tiller, 2012).

2. Early intervention for hearing loss is essential for development of language and later learning.

3. Dentition may be difficult or delayed; these children are more prone to cavities. Ongoing examination and treatment is vital.

4. Scoliosis may progress quickly for those nearing puberty—bracing is often ineffective. Early surgical fusion may provide the best option for treatment.

5. If a diagnosis has been made prenatally, operative delivery to avoid fractures and intracranial bleeding is recommended.

Achondroplasia

A. Incidence and etiology.

1. Achondroplasia occurs with a frequency of 1 in 25,000 live births (Rimoin and Tiller, 2012).

a. Most common skeletal dysplasia in humans (Lewanda et al., 2006).

2. Defect has an autosomal dominant inheritance pattern. Eighty percent are sporadic occurrences of FGFR3 (fibroblast growth factor receptor 3), representing a new mutation on chromosome 4p16.3 (Rimoin and Tiller, 2012).

a. New mutations occur in the father’s sperm and are associated with advanced paternal age (Lewanda et al., 2006).

b. Transmitted as a fully penetrant autosomal dominant trait; each person who inherits the mutant gene will show the condition (Rimoin and Tiller, 2012).

B. Clinical presentation.

1. General: small stature. Small at birth, with increasingly apparent growth deficiency secondary to failure of endochondral ossification.

2. Craniofacial: megalocephaly, small foramen magnum, low nasal bridge, flat midface, short flat nose with broad tip, anteverted nares, long philtrum, hypotelorism (Jones et al., 2013).

3. Musculoskeletal: short limbs, lumbar lordosis, mild thoracolumbar kyphosis, short tubular bones, vertebral anomalies, short trident hand, hyperextensible joints, shortened upper limbs, and flexion contractures at elbows.

C. Associated findings.

1. Mild hypotonia, especially in the trunk and extremities, with delayed milestones.

5. Upper airway is often small, leading to obstructive apnea, snoring, and serous otitis media (Rimoin and Tiller, 2012).

D. Diagnosis.

1. Chromosomal studies to confirm mutation on 4p16.3 chromosome.

1. Infants with known achondroplasia must be closely monitored for developmental delay, hypotonia, and abnormal growth patterns.

2. Unsupported sitting is associated with development of kyphosis. Infants should not be allowed to be carried in flexed positions before trunk muscle strength is adequate (Rimoin and Tiller, 2012). Most infants lose kyphosis and develop lumbar lordosis when ambulation begins.

3. Hydrocephalus may develop within the first 2 years of life. Radiologic imaging of the skull as a baseline is recommended for monitoring; monthly head circumference should be obtained and plotted to determine abnormal growth.

4. Obstructive apnea may represent a serious threat. Treatment may consist of tonsillectomy or adenoidectomy. Evaluation for foramen magnum stenosis should be done.

5. Treatment for severe bowing of the legs is often deferred until full growth has occurred. Osteotomies provide needed corrections (Jones et al., 2013).

6. Close monitoring of auditory performance is needed as shortened eustachian tubes may lead to middle ear infections and resultant hearing loss. Many infants require placement of tympanic membrane tubes.

7. Dental crowding is frequently encountered, requiring removal of one or more teeth.

8. Obesity develops toward late childhood and should be monitored closely.