Acondroplacia

UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO FACULTAD DE ESTUDIO SUPERIORES IZTACALA LICENCIATURA EN ENFERMERÍA MODULO OPTATIVO: GENÉTICA Y SALUD REPRODUCTIVA

TRABAJO PARA TERCER PARCIAL

REALIZO: HUGO HÉCTOR GARCÍA HERNÁNDEZ

#100800 ACHONDROPLASIA; ACH
Gene map locus 4p16.3 TEXT A number sign (#) is used with this entry because of evidence that achondroplasia is caused by mutation in thefibroblast growth factor receptor-3 gene (FGFR3; 134934), which is located at 4p16.3. DESCRIPTION Achondroplasia is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and midface hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, genu varum, and tridenthand. Achondroplasia is an autosomal dominant disorder; a majority of cases are sporadic, the result of a de novo mutation. CLINICAL FEATURES Whereas many conditions that cause short stature have inappropriately been called achondroplasia in the past, the phenotype of this osteochondrodysplasia is so distinctive and so easily identified clinically and radiologically at birth that confusion shouldnot occur. It is characterized by a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. Hyperextensibility of most joints, especially the knees, is common, but extension and rotation are limited at the elbow. A thoracolumbar gibbus is typically present atbirth, but usually gives way to exaggerated lumbar lordosis when the child begins to ambulate. Mild to moderate hypotonia is common, and motor milestones are usually delayed. Intelligence is normal unless hydrocephalus or other central nervous system complications arise. In 13 achondroplastic infants, Hecht et al. (1991) found that cognitive development was average and did not correlate with motordevelopment which typically was delayed. It was noteworthy that reduced mental capacity correlated with evidence of respiratory dysfunction detected by polysomnography. In children, caudad narrowing of the interpediculate distance, rather than the normal caudad widening, and a notchlike sacroiliac groove are typical radiologic features. Also in children, epiphyseal ossification centers show acircumflex or chevron seat on the metaphysis. Limb shortening is especially striking in the proximal segments, e.g., the humerus; hence the description rhizomelic ('root limb'). The radiologic features of true

achondroplasia and much concerning the natural history of the condition were presented by Langer et al. (1967) on the basis of a study of 101 cases and by Hall (1988). True megalencephalyoccurs in achondroplasia and has been speculated to indicate effects of the gene other than those on the skeleton alone (Dennis et al., 1961). Disproportion between the base of the skull and the brain results in internal hydrocephalus in some cases. The hydrocephalus may be caused by increased intracranial venous pressure due to stenosis of the sigmoid sinus at the level of the narrowed jugularforamina (Pierre-Kahn et al., 1980). Hall et al. (1982) pointed out that the large head of the achondroplastic fetus creates an increased risk of intracranial bleeding during delivery. They recommended that in the management of achondroplastic infants ultrasonography be done at birth and at 2, 4, and 6 months of age to establish ventricular size, the presence or absence of hydrocephalus, and possibleintracranial bleed. They stated the impression that some achondroplasts have only megalencephaly, others have true communicating hydrocephalus, and yet others have dilated ventricles without hydrocephalus. Nelson et al. (1988) concluded that brainstem compression is common in achondroplasia and may account in part for the abnormal respiratory function. Pauli et al. (1984) focused attention on...