Dwarfism can refer to either proportional or to non-proportional short stature. In proportional short stature in adults (generally, less than 147 cm, or 4 ft and 10 in), there is uniform reduction in body size that is either the result of an inherited trait (parental short stature), an endocrinopathy like growth hormone deficiency, or malnutrition during development. In disproportional short stature, the torso or extremities are selectively shortened and the underlying cause is achondroplasia (resulting from a mutation in FGFR3, and the cause of about 70 percent of cases of dwarfism) or another connective tissue disorder. In proportional dwarfism, cognition is normal whereas in disproportional dwarfism, cognitive ability can vary widely. It should be commented that a majority of severely cognitively delayed patients within this group of short stature fall well below average for height and weight, but there is a small group whose fully attained height is below 135 cm (4 ft and 6 in) and who stand apart by this quality alone (see Jones for Smith’s classification of dwarfs). The main syndromic types of dwarfism are as follows: 1. Nanocephalic dwarfism (Seckel bird-headed dwarfism). The uncomplimentary term bird head has been applied to individuals with a small head, large-appearing eyeballs, beaked nose, and underdeveloped chin. Such a physiognomy is not unique to any disease, but when combined with dwarfism it includes a few more or less specific syndromes. Up to 1976, approximately 25 cases had been reported, some with other skeletal and urogenital abnormalities, such as medial curvature of middle digits; occasional syndactyly of toes; dislocations of elbow, hip, and knee; premature closure of cranial sutures; and clubfoot deformity. These individuals are short at birth and remain so, living until adolescence or adulthood. Cognitive impairment is severe. The cause is a homozygous or compound heterozygous mutation in RAD3-related protein, which is also implicated in ataxia-telangectasia. At autopsy the brain is found to have a simplified convolutional pattern; one of our patients had a type of myelin degeneration similar to that of Pelizaeus-Merzbacher disease.
2. Russell-Silver syndrome. Possibly an autosomal dominant pattern of inheritance, with short stature of prenatal onset, craniofacial dysostosis, short arms, congenital hemihypertrophy (arm and leg on one side larger and longer), pseudohydrocephalic head (normal-sized cranium with small facial bones), abnormalities of genital development in one-third of cases, delay in closure of fontanels and in epiphyseal maturation, elevation of urinary gonadotropins. Some cases appear to be caused by a nonmutational modification of genes, which are nonetheless inherited (imprinting).
3. Smith-Lemli-Opitz syndrome. Autosomal recessive inheritance with microcephaly, broad nasal tip and anteverted nares, wide-set eyes, epicanthal folds, ptosis, small chin, low-set ears, enlarged alveolar maxillary ridge, cutaneous syndactyly, hypospadias in boys, short stature, subnormal neonatal activity, and normal amino acids and serum immunoglobulins. Older survivors are bereft of language and are paraparetic, with increased reflexes and Babinski signs. The hips are usually dislocated. The responsible mutation is in DHCR7. The brain is small but has not been fully examined. Two of our patients were sibling girls.