NGF-dependent neurons and neurobiology of emotions and feelings: Lessons from congenital insensitivity to pain with anhidrosis.

NGF is a well-studied neurotrophic factor, and TrkA is a receptor tyrosine kinase for NGF. The NGF-TrkA system supports the survival and maintenance of NGF-dependent neurons during development. Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive genetic disorder due to loss-of-function mutations in the NTRK1 gene encoding TrkA. Individuals with CIPA lack NGF-dependent neurons, including NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. Thus, the pathophysiology of CIPA can provide intriguing findings to elucidate the unique functions that NGF-dependent neurons serve in humans, which might be difficult to evaluate in animal studies. Preceding studies have shown that the NGF-TrkA system plays critical roles in pain, itching and inflammation. This review focuses on the clinical and neurobiological aspects of CIPA and explains that NGF-dependent neurons in the peripheral nervous system play pivotal roles in interoception and homeostasis of our body, as well as in the stress response. Furthermore, these NGF-dependent neurons are likely requisite for neurobiological processes of 'emotions and feelings' in our species.

Psychoeducational characteristics of children with hypohidrotic ectodermal dysplasia.

OBJECTIVE: Hypohidrotic ectodermal dysplasia (HED) is an X-linked hereditary disorder characterized by hypohidrosis, hypotrichosis, and anomalous dentition. Estimates of up to 50% of affected children having intellectual disability are controversial. METHOD: In a cross-sectional study, 45 youth with HED (77% males, mean age 9.75 years) and 59 matched unaffected controls (70% males, mean age 9.79 years) were administered the Kaufman Brief Intelligence Test and the Kaufman Test of Educational Achievement, and their parents completed standardized neurodevelopmental and behavioral measures, educational, and health-related information regarding their child, as well as standardized and nonstandardized data regarding socioeconomic information for their family. RESULTS: There were no statistically significant differences between the two groups in intelligence quotient composite and educational achievement scores, suggesting absence of learning disability in either group. No gender differences within or between groups were found on any performance measures. Among affected youth, parental education level correlated positively with (1) cognitive vocabulary scores and cognitive composite scores; (2) educational achievement for mathematics, reading, and composite scores. CONCLUSION: Youth affected with HED and unaffected matched peers have similar profiles on standardized measures of cognition, educational achievement, and adaptive functioning although children with HED may be at increased risk for ADHD.

Quality of life of cutaneous disease in the ectodermal dysplasias.

The ectodermal dysplasias are a complex, heritable group of syndromes that affect derivatives of ectoderm. The dermatologist plays an important role in ectodermal dysplasias as the visible defects of skin, hair, and nails are often recognized first. Our objective was to examine how quality of life relates to the degree of skin involvement in ectodermal dysplasias. Subjects (n = 42) with ectodermal dysplasias were surveyed at national and regional conferences hosted by National Foundation for Ectodermal Dysplasias on July 26 to 28, 2007 and November 17, 2007. Severity of hypohidrosis, alopecia, and fingernail involvement were measured using validated Likert scales. The quality of life was measured using the Children's Dermatology Life Quality Index in children, and the Skindex-29 and RAND Short Form-36 in adults. The severity for all subjects (n = 42) was greatest for hypohidrosis, which clinically translated into "little ability to sweat." We found that the greatest impact on quality of life was related to the actual symptoms of ectodermal dysplasias, which is not surprising as almost all participants reported skin involvement (93%), most likely related to hypohidrosis, atopic dermatitis, skin erosions and infections. The symptoms of ectodermal dysplasias may also be related to the nail involvement, as manifested by dystrophic or fragmented nails. Alopecia did not play a significant role in the quality of life burden. The challenge of providing proper skin care emphasizes the benefit of dermatologic involvement, and the need for increased recognition and enhanced awareness of the cutaneous burden in ectodermal dysplasias.

Psychological aspects of hypohidrotic ectodermal dysplasia.

There is little information on the psychologic aspects of HED. In particular, there is insufficient evidence to support or dispute the claim that the intelligence of persons with HED is dissimilar to that of the general population. Impressions of frequent mental retardation may arise from patients suffering brain damage following high fever and from our biases against the physically unattractive. A small number of adults with HED have been reported to hold a relatively wide range of jobs, and an even smaller number have been reported with educational and occupational achievement that is predictive of bright average to superior intellectual functioning, but even less evidence is available here. Chronic illness and handicaps exert a toll on the patient and the family. There appears to be greater maladjustment among the families of chronically ill children, but this differs according to the type of illness, and we do not know how this affects the HED child and his/her family. Still, the HED family is exposed to some unique stresses: having always to take into account the ambient temperature regardless of their planned activity; responding to cruel stares and remarks when out in public; and dealing with the problem of broken, lost, or merely publicly discovered dentures. On the other hand, some children apparently benefit from having a sib with a disability. Families react in a variety of ways to a disability, and their reaction may interact with the child's temperament to affect emotional development for better or worse. However, the existence of HED does not insure either normal or inadequate emotional adjustment, and parents should be advised of this. As difficult as it may be, this may also be the time for the pediatrician to say "I don't know." Parents can be told that each child, not just those with HED, should be provided a warm and supportive environment congruent with his/her unique style, in order to facilitate emotional development. They should also be advised of the probable emotional benefits of early prosthetic care with wigs and dentures. When this is either not possible or not sufficient, professional guidance should be sought. Psychotherapy or counseling can be obtained for the child, a parent, or for the entire family. While some familiarity with HED may be helpful, it is not essential, and is far less important than finding a competent professional with whom the family is comfortable. As far as obtaining the information we need, a series of systematic investigations appears to be called for.(ABSTRACT TRUNCATED AT 400 WORDS)