Fetal Skeleton

Sonographic Evaluation of Skeletal Dysplasias

The patient whose fetus is at risk for a skeletal dysplasia is commonly referred to a maternal-fetal center for genetic counseling and a targeted ultrasound. Although many skeletal dysplasias are inherited, sporadic occurrences and new mutations do occur, so it is important to screen for skeletal dysplasias as part of every obstetric ultrasound examination. Most prenatally diagnosed skeletal dysplasias occur in association with polyhydramnios or other fetal anomalies or when there is a risk for recurrence.

When a skeletal dysplasia is suspected, the protocol of the obstetric ultrasound examination should be adjusted to include the following criteria:

• 1.

  Assess limb shortening. All long bones should be measured. A skeletal dysplasia is suspected when limb lengths are more than 2 standard deviations below the mean ( Tables 65.2 and 65.3 ).

  Table 65.2

  Length of the Bones of the Leg: Normal Values (mm)

  From Jeanty P, Romero R, editors. Obstetrical Ultrasound . New York: McGraw-Hill; 1984.

  Week	Tibia Percentile			Fibula Percentile
  	5th	50th	95th	5th	50th	95th
  12	—	7	—	—	6	—
  13	—	10	—	—	9	—
  14	7	12	17	6	12	19
  15	9	15	20	9	15	21
  16	12	17	22	13	18	23
  17	15	20	25	13	21	28
  18	17	22	27	15	23	31
  19	20	25	30	19	26	33
  20	22	27	33	21	28	36
  21	25	30	35	24	31	37
  22	27	32	38	27	33	39
  23	30	35	40	28	35	42
  24	32	37	42	29	37	45
  25	34	40	45	34	40	45
  26	37	42	47	36	42	47
  27	39	44	49	37	44	50
  28	41	46	51	38	45	53
  29	43	48	53	41	47	54
  30	45	50	55	43	49	56
  31	47	52	57	42	51	59
  32	48	54	59	42	52	63
  33	50	55	60	46	54	62
  34	52	57	62	46	55	65
  35	53	58	64	51	57	62
  36	55	60	65	54	58	63
  37	56	61	67	54	59	65
  38	58	63	68	56	61	65
  39	59	64	69	56	62	67
  40	61	66	71	59	63	67

  Table 65.3

  Length of the Bones of the Arm: Normal Values (mm)

  From Jeanty P, Romero R, editors. Obstetrical Ultrasound . New York: McGraw-Hill; 1984.

  Week	Ulna Percentile			Radius Percentile
  	5th	50th	95th	5th	50th	95th
  12	—	7	—	—	7	—
  13	5	10	15	6	10	14
  14	8	13	18	8	13	17
  15	11	16	21	11	15	20
  16	13	18	23	13	18	22
  17	16	21	26	14	20	26
  18	19	24	29	15	22	29
  19	21	26	31	20	24	29
  20	24	29	34	22	27	32
  21	26	31	36	24	29	33
  22	28	33	38	27	31	34
  23	31	36	41	26	32	39
  24	33	38	43	26	34	42
  25	35	40	45	31	36	41
  26	37	42	47	32	37	43
  27	39	44	49	33	39	45
  28	41	46	51	33	40	48
  29	43	48	53	36	42	47
  30	44	49	54	36	43	49
  31	46	51	56	38	44	50
  32	48	53	58	37	45	53
  33	49	54	59	41	46	51
  34	51	56	61	40	47	53
  35	52	57	62	41	48	54
  36	53	58	63	39	48	57
  37	55	60	65	45	49	53
  38	56	61	66	45	49	54
  39	57	62	67	45	50	54
  40	58	63	68	46	50	55

• 2.

  Assess bone contour. Thickness, assessment for abnormal bowing or curvature, fractures, and a ribbon-like appearance should be performed.

• 3.

  Estimate degree of ossification. Decreased attenuation of the bones with decreased shadowing suggests hypomineralization. Special attention should be focused toward this assessment of the cranium, spine, ribs, and long bones.

• 4.

  Evaluate the thoracic circumference and shape. A long, narrow chest or a bell-shaped chest may be indicative of specific dysplasias.

• 5.

  Survey for coexistent hand and foot anomalies, such as talipes and polydactyly.

• 6.

  Evaluate the face and profile for facial clefts, frontal bossing, micrognathia, hypertelorism, and other facial anomalies that may be associated with skeletal dysplasias.

• 7.

  Survey for other associated anomalies, such as hydrocephaly, heart defects, and nonimmune hydrops.

The manifestation of skeletal dysplasias varies based on the specific dysplasia, and three-dimensional ultrasound may aid in the diagnosis. First trimester assessment may present with an increased nuchal translucency, which increases the risk for lethality, and chorionic villus sampling may provide important diagnostic information regarding the type of skeletal dysplasia. In addition, long bones are affected in different patterns ( Fig. 65.1 ) according to the dysplasia. Rhizomelia is shortening of the proximal bone segment (humerus and femur). Mesomelia refers to shortening of the middle segments (radius/ulna and tibia/fibula). Micromelia describes the shortening of the entire extremity. Sonographic examination of the long bones should include an assessment to define whether there is segmental shortening or micromelia, because this will aid in the diagnosis. Three-dimensional evaluation may provide further definition of the abnormality.

Thanatophoric Dysplasia

Thanatophoric dysplasia is the most common lethal skeletal dysplasia and occurs in 1 in 20,000 to 40,000 live births ( Fig. 65.2 ). The term thanatophoric comes from the Greek word thanatos , which means death personified . The two main subdivisions of thanatophoric dysplasia are types I and II. Type I is characterized by short, curved femurs and flat vertebral bodies. Type II is characterized by straight, short femurs, flat vertebral bodies, and a cloverleaf skull. Most cases of thanatophoric dysplasia are sporadic occurrences and the result of mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Prenatal molecular analysis can aid in making the definitive diagnosis.

The prognosis for thanatophoric dysplasia is extremely grim. It is considered a lethal anomaly, with most infants dying shortly after birth as a result of pulmonary hypoplasia, which results from the narrow thorax.

Achondroplasia

Achondroplasia is the most common nonlethal skeletal dysplasia and occurs in approximately 1 in 10,000 to 30,000 live births. It results from decreased endochondral bone formation, which produces short, squat bones. It is most commonly the result of a spontaneous mutation but can also be transmitted in an autosomal fashion. Advanced paternal age increases the risk for this dysplasia.

The prognosis for achondroplasia depends on the form. Heterozygous achondroplasia , inherited from one parent, has a good survival rate with normal intelligence and a normal life span. Health problems may include neurologic complications that may require orthopedic or neurologic surgical intervention. Homozygous achondroplasia , inherited from two parents, is considered lethal, with most infants dying shortly after birth from respiratory complications. With this form, sonographic findings are more severe and include a narrow thorax.

Achondrogenesis

Achondrogenesis is a rare, lethal skeletal dysplasia occurring in 1 in 40,000 births and is caused by cartilage abnormalities that result in abnormal bone formation and hypomineralization. The two types of achondrogenesis are types I (Parenti-Fraccaro) and II (Langer-Saldino). Type I is considered more severe and is transmitted in an autosomal recessive mode, whereas type II is less severe, is more common, and is the result of a spontaneous mutation.

The prognosis for achondrogenesis is grim. It is a lethal abnormality with infants either being stillborn or dying shortly after birth from pulmonary hypoplasia.

Sonographic Findings

The sonographic features ( Figs. 65.4–65.6 ) of achondrogenesis include the following:

• Severe micromelia

• Decreased or absent ossification of the spine

• Macrocephaly

• Short trunk

• Short thorax and short ribs

• Micrognathia

• Polyhydramnios

• Hydrops possibly identified

Osteogenesis Imperfecta

Osteogenesis imperfecta is a rare disorder of collagen production leading to brittle bones, blue sclera, and manifestations in the teeth, skin, and ligaments. It has been linked to mutations in the COL1A1 and COL1A2 genes. There are four classifications, types I to IV. Types I and IV are the mildest forms, and it would be unlikely that a diagnosis would be made in utero. Types I and IV are transmitted in an autosomal dominant fashion. Type III is a severe form that may be transmitted in an autosomal dominant or autosomal recessive manner. Type II ( Fig. 65.7 ) is considered the most severe form of osteogenesis imperfecta, having a lethal outcome. It is inherited in an autosomal dominant or autosomal recessive fashion or may result from a spontaneous mutation.

The prognosis for osteogenesis imperfecta depends on the type. Children with types I and IV may have multiple fractures during childhood and may be short. Type I children may also have kyphoscoliosis and deafness. Because of the severity of the brittle bones and multiple fractures, osteogenesis imperfecta type III may produce significant disabilities with progressive deformities of the long bones and spine. Infants with type II usually die shortly after birth because of respiratory complications.