4. Rubinstein-Taybi syndrome. Microcephaly but no craniosynostosis, downward palpebral slant, heavy eyebrows, beaked nose with nasal septum extending below alae nasi, mild retrognathia, “grimacing smile,” strabismus, cataracts, obstruction of nasolacrimal canals, broad thumbs and toes, clinodactyly, overlapping digits, excessive hair growth, hypotonia, lax ligaments, stiff gait, seizures, hyperactive tendon reflexes, absence of corpus callosum, mental retardation, and short stature. This dominantly inherited disease is a result of disruption of so-called CREB-binding protein, a nuclear protein necessary for gene expression that is modulated by cyclic adenosine monophosphate (cAMP).
5. Pierre Robin syndrome. Possible autosomal recessive pattern of inheritance with microcephaly but no craniosynostosis, small and symmetrically receded chin, glossoptosis (tongue falls back into pharynx), cleft palate, flat bridge of nose, low-set ears, cognitive impairment, and congenital heart disease in half the cases. Camptomelia (bent bones) and diastrophic dwarfism (short limbs) are common.
6. DeLange syndrome (Cornelia DeLange syndrome). This phenotype shows some degree of variability but the essential diagnostic features are intrauterine growth retardation and stature falling below the third percentile at all ages, microbrachycephaly, generalized hirsutism and synophrys (eyebrows that meet across the midline), anteverted nostrils, long upper lip, and skeletal abnormalities (flexion of elbows, webbing of second and third toes, clinodactyly of fifth fingers, transverse palmar crease). All are moderately or, as often, severely cognitively impaired, which, with the above craniofacial abnormalities, is diagnostic. It has been said, and it has been our experience, that many of these patients are prone to have a bad disposition, manifested by biting and spitting. Over half of cases are due to mutations in the NAPBL gene; the others involve SMC1A or SMC3.
7. Smith-Magenis syndrome. This is caused by deletions on chromosome 17, in which there is learning disability, severe behavioral problems (violence and self-injury), hyperactivity, deafness, and ocular abnormalities.
It is not surprising that skin and nervous system should share in pathologic states that impair development, as both have a common ectodermal derivation. Nevertheless, it is difficult to find a common theme in the diseases that affect both organs. In some instances, it is clear that ectoderm has been malformed from early intrauterine life; in others, a number of nondevelopmental acquired diseases of skin may have been superimposed. For reasons to be discussed later in this chapter, neurofibromatosis, tuberous sclerosis, and Sturge-Weber encephalofacial angiomatosis must be set apart in a special category of disease termed phakomatoses.
Hemangiomas of the skin are without doubt the most frequent cutaneous abnormalities present at birth, and usually they are entirely innocent. Many recede in the first months of life. However, an extensive vascular nevus located in the territory of the trigeminal nerve—and sometimes in other parts of the body as well—causes permanent disfigurement and usually portends an associated and topographically underlying cerebral lesion (Sturge-Weber syndrome).
Other neurocutaneous diseases are summarized below. A more complete review of these diseases will be found in the 1987 monograph by Gomez. The importance of recognizing the cutaneous abnormalities relates to the fact that the nervous system is usually abnormal, and often the skin lesion appears before the neurologic symptoms are detectable. Thus the skin lesion becomes a predictor of potential neurologic involvement.