Genetic drift. The ancient Egyptian dwarfs of the pyramids: the high official and the female worker.

The existence of dwarfism is amply documented in ancient Egypt due to the rich biological and artistic legacies. In previous articles published in this journal, I discussed the roles of people with skeletal dysplasia in ancient Egyptian civilization. In this article I, along with my Egyptian and American colleagues, describe two skeletons of dwarfs that date to 2700-2184 BCE and were unearthed from a funerary complex near the Great Pyramids in Giza. The first skeleton belongs to a high official, Per-ni-ankh-w, who died between 45 and 50 years of age. His statue is on display in the Egyptian Museum of Cairo. The second skeleton belongs to a pregnant female worker found with a fetus in situ. Her estimated age at death was 25-30 years. She most likely died during childbirth due to a small pelvic outlet as supported by her narrow sacrum. The fetal bones appear normal. Radiological examination of both skeletons confirmed the clinical diagnosis of achondroplasia. Ancient Egyptians concerned themselves with the search for spiritual fulfillment through the tradition of moral teachings. Amenemope, a wise man who lived during the reign of Amenhotep III (1391-1354 BCE), advocated respect toward individuals with disabilities: Do not jeer at a blind man nor tease a dwarf, Neither interfere with the condition of a cripple. Do not taunt a man who is in the hand of God, Nor scowl at him if he errs. In summary, artistic, biological, and written resources indicate that dwarfs were well integrated in ancient Egyptian society.

Methotrexate and misoprostol teratogenicity: further expansion of the clinical manifestations.

We describe a boy who was exposed to misoprostol and methotrexate in the first trimester of gestation as a result of a failed medical abortion. He presented with severe growth retardation, skull defects, proptotic eyes, cleft palate, and severe micrognathia. There were bilateral defects of the upper and lower extremities, missing and hypoplastic ribs, and undescended testicles. He had clinical features of pulmonary hypoplasia with severe persistent pulmonary hypertension and remained ventilator-dependent until he expired. An autopsy revealed brain anomalies consistent with arrhinencephaly. Methotrexate is frequently used in conjunction with misoprostol to induce medical abortion, an off-label use as abortifacient. Both of these medications are well-established teratogens and have an X classification during pregnancy. Data from eight patients who were exposed to both medications in the first trimester indicate a significant teratogenic risk to the developing fetus. Reported anomalies include growth retardation, absence or hypoplasia of the frontal bones, craniosynostosis, large fontanelle, ocular hypertelorism, short palpebral fissures, wide nasal bridge, malformed and low-set ears, and micrognathia. Skeletal anomalies are frequent consisting of syndactyly, mesomelic shortening of the forearms, missing ribs, dislocated hips, and talipes equinovarus. The findings in our case are consistent with the pattern of abnormalities that have been reported in the literature. In addition, our patient had severe pulmonary hypoplasia and arrhinencephaly, anomalies that have not been described previously. This case adds to the documentation of the teratogenic effects of methotrexate and misoprostol on the developing fetus.

Genetic Drift. The ancient Egyptian dwarfs of the Walters Art Museum.

The ancient Egyptians left an impressive artistic legacy documenting many aspects of their society including the existence of dwarfs as highly valued members. In previous publications in the Journal, I discussed dwarfs and skeletal dysplasia in ancient Egypt. In this study, I examined the ancient Egyptian representations of dwarfs of the Walters Art Museum in Baltimore, Maryland. One of the highlights of the collection is a group of five ivory figurines from Predynastic Times (pre 3500-3100 BCE) depicting a couple, a man with a child, and two females. Representations from other periods include ordinary as well as dwarf deities. The dwarf gods, Bes and Ptah, are frequently depicted holding or biting snakes or standing on crocodiles symbolizing their ability to ward off dangers. A couple of statuettes from the Greco-Roman Period that, in contrast to earlier Egyptian Periods, depict harsh physical anomalies, twisted bodies, and facial pain. The artistic impression can be interpreted as either tragic or humorous. The grotesque depiction of dwarfs during the Greco-Roman Period in ancient Egypt is believed to be due to a greater infusion of Hellenistic influence. This study provides a microcosm of the legacy of dwarfs in ancient Egypt and supports the premise that dwarfs were accepted and integrated in the ancient Egyptian society, and with a few exceptions, their disorder was not depicted as a physical handicap.

Skeletal dysplasia in ancient Egypt.

The ancient Egyptian civilization lasted for over 3000 years and ended in 30 BCE. Many aspects of ancient Egyptian culture, including the existence of skeletal dysplasias, and in particular achondroplasia, are well known through the monuments and records that survived until modern times. The hot and dry climate in Egypt allowed for the preservation of bodies and skeletal anomalies. The oldest dwarf skeleton, the Badarian skeleton (4500 BCE), possibly represents an epiphyseal disorder. Among the remains of dwarfs with achondroplasia from ancient Egypt (2686-2190 BCE), exists a skeleton of a pregnant female, believed to have died during delivery with a baby's remains in situ. British museums have partial skeletons of dwarfs with achondroplasia, humeri probably affected with mucopolysaccharidoses, and a skeleton of a child with osteogenesis imperfecta. Skeletal dysplasia is also found among royal remains. The mummy of the pharaoh Siptah (1342-1197 BCE) shows a deformity of the left leg and foot. A mummified fetus, believed to be the daughter of king Tutankhamun, has scoliosis, spina bifida, and Sprengel deformity. In 2006 I reviewed the previously existing knowledge of dwarfism in ancient Egypt. The purpose of this second historical review is to add to that knowledge with an expanded contribution. The artistic documentation of people with skeletal dysplasia from ancient Egypt is plentiful including hundreds of amulets, statues, and drawing on tomb and temple walls. Examination of artistic reliefs provides a glance of the role of people with skeletal dysplasia and the societal attitudes toward them. Both artistic evidence and moral teachings in ancient Egypt reveal wide integration of individuals with disabilities into the society.

Health supervision visits among SSI-eligible children in the D.C. Medicaid program: a comparison of enrollees in fee-for-service and partially capitated managed care.

Managed care plans that involve some form of capitation may have adverse effects on children with special health care needs because the financial incentives to control costs may result in under-treatment and restrict access to expensive services and specialty providers. Proponents highlight the advantages of a managed care model, including case management and coordination of services. In light of this debate, only a few state Medicaid programs have implemented a managed care option for children with special health care needs. This study evaluates the effects of plan choice (partially capitated managed care versus fee-for-service) on whether children with disabilities eligible for Supplemental Security Income (SSI) and enrolled in the District of Columbia's Medicaid program are in compliance with the guidelines for health supervision visits established by the American Academy of Pediatrics (AAP). Our findings, based on five years of claims data, show that SSI-eligible children with disabilities enrolled in a partially capitated managed care plan are significantly more likely to be in compliance with the AAP guidelines for health supervision visits compared to their fee-for-service counterparts. Moreover, we find that selection due to unobservable characteristics does not significantly bias the estimated program effects.

Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta.

A recessive form of severe osteogenesis imperfecta that is not caused by mutations in type I collagen has long been suspected. Mutations in human CRTAP (cartilage-associated protein) causing recessive bone disease have been reported. CRTAP forms a complex with cyclophilin B and prolyl 3-hydroxylase 1, which is encoded by LEPRE1 and hydroxylates one residue in type I collagen, alpha1(I)Pro986. We present the first five cases of a new recessive bone disorder resulting from null LEPRE1 alleles; its phenotype overlaps with lethal/severe osteogenesis imperfecta but has distinctive features. Furthermore, a mutant allele from West Africa, also found in African Americans, occurs in four of five cases. All proband LEPRE1 mutations led to premature termination codons and minimal mRNA and protein. Proband collagen had minimal 3-hydroxylation of alpha1(I)Pro986 but excess lysyl hydroxylation and glycosylation along the collagen helix. Proband collagen secretion was moderately delayed, but total collagen secretion was increased. Prolyl 3-hydroxylase 1 is therefore crucial for bone development and collagen helix formation.

Dwarfs in ancient Egypt.

Ancient Egypt was one of the most advanced and productive civilizations in antiquity, spanning 3000 years before the "Christian" era. Ancient Egyptians built colossal temples and magnificent tombs to honor their gods and religious leaders. Their hieroglyphic language, system of organization, and recording of events give contemporary researchers insights into their daily activities. Based on the record left by their art, the ancient Egyptians documented the presence of dwarfs in almost every facet of life. Due to the hot dry climate and natural and artificial mummification, Egypt is a major source of information on achondroplasia in the old world. The remains of dwarfs are abundant and include complete and partial skeletons. Dwarfs were employed as personal attendants, animal tenders, jewelers, and entertainers. Several high-ranking dwarfs especially from the Old Kingdom (2700-2190 BCE) achieved important status and had lavish burial places close to the pyramids. Their costly tombs in the royal cemeteries and the inscriptions on their statutes indicate their high-ranking position in Egyptian society and their close relation to the king. Some of them were Seneb, Pereniankh, Khnumhotpe, and Djeder. There were at least two dwarf gods, Ptah and Bes. The god Ptah was associated with regeneration and rejuvenation. The god Bes was a protector of sexuality, childbirth, women, and children. He was a favored deity particularly during the Greco-Roman period. His temple was recently excavated in the Baharia oasis in the middle of Egypt. The burial sites and artistic sources provide glimpses of the positions of dwarfs in daily life in ancient Egypt. Dwarfs were accepted in ancient Egypt; their recorded daily activities suggest assimilation into daily life, and their disorder was not shown as a physical handicap. Wisdom writings and moral teachings in ancient Egypt commanded respect for dwarfs and other individuals with disabilities.

Neonatal toxicity and transient neurodevelopmental deficits following prenatal exposure to lithium: Another clinical report and a review of the literature.

I report the case of an infant girl who was exposed to lithium during gestation and her follow-up at the age of 1 year. She presented with transient neurodevelopmental deficits including lethargy, hypotonia, and poor oral feeding ability in the neonatal period. She required supportive treatment and made gradual improvement in neurologic functioning. On examination at the age of 1 year, physical findings and psychomotor development were normal. The English literature from 1978 to 2004 is reviewed. A total of 30 patients who were exposed to lithium during gestation with adequate clinical description were identified. A significant number of these babies presented with neurodevelopmental deficits and depressed neurological status including hypotonia, respiratory distress syndrome, cyanosis, lethargy, and weak suck and Moro reflexes in the neonatal period. The majority of these abnormalities resolved and most babies made full recovery. Other abnormalities were structural as well as functional involvement of the cardiovascular system, macrosomia, prematurity, jaundice, diabetes insipidus, and involvement of the thyroid gland. While the use of lithium during pregnancy does not appear to significantly increase the risk of congenital anomalies, it is frequently associated with perinatal complications and reversible neonatal toxicity. Suggested guidelines for appropriate monitoring of infants and breast-feeding of exposed babies are presented. In addition, prenatal surveillance of women with bipolar disorders who are being treated with lithium is briefly discussed.

Segregation of a t(1;3) translocation in multiple affected family members with both types of adjacent-1 segregants.

A subtle balanced translocation involving the terminal regions of 1q and 3p was identified in a large family by high-resolution karyotype analysis and confirmed by fluorescence in situ hybridization (FISH) analysis. In this family, segregation of a balanced t(1:3)(q42.3;p25) chromosome translocation led to two types of viable unbalanced complements. The proband inherited the derivative chromosome 3, resulting in partial trisomy of 1q and partial monosomy of 3p. A paternal uncle and cousin had the reciprocal rearrangement with a derivative of chromosome 1, resulting in partial monosomy for 1q and partial trisomy for 3p. While profound mental and physical retardation and congenital heart defects were characteristics for both rearrangements, facial dysmorphism was quite distinct for each imbalance. Individuals who had the derivative chromosome 3 had a long face, wide eyebrows, small palpebral fissures, hypertelorism, prominent glabella, a large tip of the nose, long philtrum with thin upper lip, and low set-ears. In contrast, family members with the derivative of chromosome 1 had a tall forehead with bifrontal narrowing, full and large cheeks, and large simple ears. Since the translocated segments are small and approximately equal in size in this family, it is not surprising that viability was seen in individuals with both types of adjacent-1 segregation. In this kindred, the ratio of normal to abnormal individuals born to balanced carriers is believed to be about 1:1.5. This suggests that the recurrence risk for carriers is 50%.

Survey of nursing and medical profile prior to deinstitutionalization of a population with profound mental retardation.

During the planning stages of deinstitutionalization, the importance of nursing services must be recognized and given priority consideration in the community placement of persons with serious developmental disabilities. The objective of this study was to survey the medical and nursing profile of a group of nonambulatory, institutionalized individuals with profound mental retardation in anticipation of their nursing and medical needs in the community. Data were collected from the Individual Habilitation Plans of 55 individuals who had resided in a residential facility for individuals with mental retardation and were scheduled for community placement Serious medical problems in decreasing frequency were constipation (96%), seizure disorder (70%), poor dental hygiene (67%), cerebral palsy (62%), scoliosis (61%), contractions (41%), aspiration (44%), skin lesions (40%), and dysphagia (22%). Considering the complexity of health issues encountered in this population, adequate nursing and medical planning are critical to the wellness and successful community placement of a population with special needs.