Cornelia de Lange Syndrome / Maple Syrup Urine Disease / Rubinstein-Taybi Syndrome: etiologies and indicators: Part 1.
The purpose of this three-part series is to share information regarding the etiology, indicators, considerations, and techniques for teaching physical education, with suggestions for activities when dealing with individuals with Cornelia de Lange Syndrome Cornelia de Lange Syndrome aka CdLS is a little known genetic disorder that can lead to severe developmental anomalies. It affects both the physical and intellectual development of a child. Exact incidence is unknown, but is estimated at 1 in 10,000 to 30,000. , Maple Syrup Urine Disease ma·ple syr·up urine disease
A hereditary metabolic disorder due to a deficiency of decarboxylase enzyme that leads to elevated concentrations of leucine, isoleucine, and valine in the blood and urine, characterized by the urine having an odor , and Rubinstein-Taybi Syndrome.
Cornelia de Lange Syndrome (CdLS)
In 1933, the Dutch doctor Cornelia de Lange described two affected infant girls, under the designation Typus degenerative Amstelodamensis, after the city from which her first case originated (Filippi. 1989). In the 1930s the condition was also recorded under Amsterdam dwarf, even though dwarfism dwarfism, condition in which an animal or plant is less than normal in size and lacks the capacity for normal growth. Dwarfism is deliberately produced and perpetuated in certain species (e.g., in breeding miniature dogs and cultivating dwarf plants). is not a variable in this disorder (Filippi, 1989). Other individuals have used the term Brachmann de Lange Syndrome to designate this disorder (Filippi, 1989: Hawley, Jackson, & Kurnit, 1985: Mosher, Schulte, Kaplan, Buehler, & Sanger, 1985: Opitz, 1985).
After de Lange's reported cases, only 21 cases in the next 30 years were reported in Europe (Filippi, 1989). in 1963, information about the first English and American cases of the syndrome was published (Ptacek, Opitz, Smith, Gerritsen, & Waisman, 1963: Schlesinger, Clayton, Bodian, & Jones, 1963: Jervis, & Stimson, 1963). Since Filippe (1989) reported, additional cases were identified in France, Italy, and Austria. There are possibly many more individuals with CdLS around the world than those associated with the Cornelia de Lange Syndrome Foundation. As of 1993-1994, the Cornelia de Lange Syndrome Foundations reported 309 individuals and their families from the United States, Australia, Canada, Germany, Switzerland, United Kingdom, and West Indies who were members of the Foundation (Cornelia de Lange Syndrome Foundation, 1994).
According to Cameron and Kelly (1988), CdLS is a relatively common disorder, with an estimated prevalence of l in 10,000 births. Diagnosis of this syndrome is based on growth, mental retardation, microbrachycephaly, and hirsutism Hirsutism Definition
Excessive growth of facial or body hair in women is called hirsutism.
Hirsutism is not a disease. The condition usually develops during puberty and becomes more pronounced as the years go by. . Diagnosis is usually made by a specialist in genetics, after completing a thorough medical evaluation, including family history, physical examination, laboratory tests, x-rays, and chromosome analysis.
At this time there are no reliable biochemical or chromosome markers for identification (Hawley et al., 1985). However, the most current information from geneticists indicates the possibility that CdLS is caused by a faulty mutant gene, probably on chromosome 3 (Cornelia de Lange Syndrome Foundation, 1994). Children with CdLS can be born into any family. The syndrome does not discriminate according to race, age of parents, religion, or socio economic status (Cornelia de Lange Syndrome Foundation, 1994).
Cornelia de Lange Syndrome (CdLS) is a disorder causing a delay in physical, intellectual, and language development (CdLS Foundation, 1993). Indicators used by medical professionals to diagnosis CdLS according to the CdLS Foundation (1993) include:
* Birth weight and birth length. Average birth weights reported ranged from one pound, two ounces to ten pounds; average birth length was approximately 18 inches.
* Higher incidence of major upper limb malformation malformation /mal·for·ma·tion/ (-for-ma´shun)
1. a type of anomaly.
2. a morphologic defect of an organ or larger region of the body, resulting from an intrinsically abnormal developmental process. . Although it appeared babies born under five pounds seemed to have a "higher incidence of major upper limb malformations" and start walking at a later age, there was no scientific data to indicate babies with low birth weight were more profoundly affected. The reverse was also true in babies who weighed more than five pounds at birth. There was no firm evidence birth weight was the only indicator for a child's prognosis.
* Mental retardation (developmental delay). The vast majority of individuals diagnosed as having CdLS were mentally retarded, with the degree of metal retardation ranging from mild to profound, and reported IQs from 30 to 85 (average 53). Although many individuals born after 1980 were reported to have higher IQ scores, reasons for this increase needs further study. Early intervention services, as well as increased diagnosis of individuals more mildly affected played important roles in explaining these results. Although mental retardation was generally considered essential for a diagnosis of CdLS, there have been instances of adults and children with CdLS with normal and borderline intelligence.
* Head and facial features. Head and facial features most commonly associated with the syndrome include small head size (microcephaly microcephaly /mi·cro·ceph·a·ly/ abnormal smallness of the head.microcephal´ic
Abnormal smallness of the head. Also called nanocephaly. ), thin eyebrows often meeting at the midline mid·line
A medial line, especially the medial line or plane of the body.
n the line equidistant from bilateral features of the head. (synophrys), long eyelashes, short upturned nose, thin downturned lips, low-set ears, and high arched palate or cleft palate.
* Other indicators. These may include language delay, even in the most mildly-affected, delayed growth and small stature, low-pitched cry, small hands and feet, in-curved fifth fingers (clinodaetyl), simian creases, excessive body hair (hirsutism), partial joining of second and third toes, and wide-spaced nipples.
Other medical concerns may include gastro-esopbageal reflux and feeding difficulties, seizures, heart defects, eye involvement; ear, nose and throat problems; bowel abnormalities, undescended testes, and purplish discoloration of the skin (eutis marmorata). Limb abnormalities, including missing limbs or portions of limbs (usually fingers, hands, or forearms), had been reported.
Several authors mentioned hearing and speech difficulties (Cameron & Kelly, 1988; Halal ha·lal Islam
Meat that has been slaughtered in the manner prescribed by the shari'a.
1. Of or being meat slaughtered in the prescribed way: a halal butcher; a halal label. & Silver, 1992; Sataloff, Spiegel, Hawkshaw Hawkshaw
implacable detective with photographic memory. [Br. Lit.: The Ticket-of-Leave Man, Barnhart, 546]
See : Sleuthing , Epstein, & Jackson, 1990; Goodban, 1993; Kline, Stanley, Belevieh, Brodsky, Barr, & Jackson, 1993). Sataloff et al. (1990) indicated hearing loss might be caused by problems in the ear canal, middle ear, or inner ear. Ear canals are commonly small in CdLS children, and may become blocked, producing hearing loss. Inner ear difficulties involve the nerve for hearing. Middle ear abnormalities are usually due to dysfunction of the bones or ear fluid common in individuals with CdLS (Sataloff, 1993). These hearing loss difficulties cause communication and learning problems (Sataloff et al., 1990).
Menyuk (1980) stated more than 50% of these individuals examined had chronic otitis media Chronic otitis media
Inflammation of the middle ear with signs of infection lasting three months or longer.
Mentioned in: Myringotomy and Ear Tubes
chronic otitis media , another known cause of language delay. According to Sataloff et al. (1990), if these problems were not corrected prior to 3 years of age, development of language could be hindered, because this is the time frame the nervous system is most ready to receive, process, and store auditory information. This might explain some attention problems reported with individuals having CdLS (Halal & Silver, 1992).
Many authors reported delayed gross motor skills (Cameron & Kelly, 1988; Halal & Silver, 1992; Hawley et al., 1985; Kline et al., 1993; Meinecke & Hayek, 1990; Mosher et al., 1985; Motl and Opitz, 1971; Opitz, 1985); however, none of these authors presented reasons for these delays. Halal and Silver (1992) reported abnormal gait and inefficient hopping patterns. Some of these difficulties in gait and inefficient hopping patterns might be due to small foot and hand size or webbing of appendages reported by Opitz (1985). Balance and coordination might also be factors due to middle ear problems previously discussed (Cameron & Kelly, 1988). Halal and Silver (1992) reported brisk deep tendon reflexes.
Maple Syrup Urine Disease
In 1954, Menkes, Hurst, and Craig (1954), described a new syndrome, by reporting four infants in one family who succumbed to a progressive neurological disorder in the first week of life. Menkes, Hurst, and Craig also reported the urine of all four infants had an odor similar to that of maple syrup. Since that time what is commonly referred to as Maple Syrup Urine Disease (MSUD MSUD maple syrup urine disease.
MSUD Maple sugar urine disease, see there ) had also been reported in the literature as Branch-Chain Ketoaciduria (BCKA BCKA Branched-Chain Keto-Acid ) and Branch-Chain Z Ketoacid Dehydrogenase dehydrogenase /de·hy·dro·gen·ase/ (de-hi´dro-jen-as?) an enzyme that catalyzes the transfer of hydrogen or electrons from a donor, oxidizing it, to an acceptor, reducing it.
n. (BCKD BCKD Branched-Chain Alpha-Keto Acid Dehydrogenase (deficiency) ) deficiency. MSUD was considered to be very rare, with an incidence ranging from one in 225,000 births (Potashnik, Carmi, Sorer, Bashan & Abeliovich, 1987) to one in 50,000 births (Foster, 1989). McMahon and MacDonnell (1993) reported incidence in the U.S. to be one in 216,000 births; however, in the inbred in·bred
1. Produced by inbreeding.
2. Fixed in the character or disposition as if inherited; deep-seated.
said of offspring produced by inbreeding. Mennonite population incidence was as high as one in 760 births.
MSUD is caused by a block in breakdown of the three-branched chain amino acids (BCAAs), leucine leucine (l`sēn), organic compund, one of the 20 amino acids commonly found in animal proteins. , isoleucine isoleucine (ī'səl`sēn), organic compound, one of the 20 amino acids commonly found in animal proteins. , and valine valine (văl`ēn), organic compound, one of the 22 α-amino acids commonly found in animal proteins. Only the l-stereoisomer appears in mammalian protein. (Northrup, Siegman, & Hebert, 1993). Each parent of a child with MSUD carries a defective recessive gene for MSUD, along with a normal gene (Foster, 1989). According to information provided by Brubacker (1993), "the parents of a child with MSUD have a 1 in 4 chance during each pregnancy that the baby will receive a defective gene from each parent and have MSUD; a 2 in 4 chance the baby will receive one defective and one normal gene becoming a carrier of MSUD; a 1 in 4 chance that the baby will receive two normal genes."
According to Snyderman (1988) there do not seem to be any racial considerations for this disease, since it had been observed in white, black, Jewish, and oriental families. It had been observed in the United States, Great Britain, France, Switzerland, Germany, Norway, Italy, Morocco, Syria, India, Israel, and Japan. Parents of a child with whom the writer works also reported high incidences among the Greek population. Subramanyam, Qadri, Dhalla, and Ozand (1990) reported an alarmingly high incidence of MSUD in the Middle East.
Children with MSUD appear normal at birth; however, by the end of the first week of life progressive deterioration, anorexia, a shrill cry, abnormal movements, hypertonicity hypertonicity /hy·per·to·nic·i·ty/ (-to-nis´i-te) the state or quality of being hypertonic.
the state or quality of being hypertonic. alternating with hypotonia hypotonia /hy·po·to·nia/ (-ton´e-ah) diminished tone of the skeletal muscles.
1. Reduced tension or pressure, as of the intraocular fluid in the eyeball.
2. , loss of primitive reflexes, irregular breathing with respiratory pauses, coma, apnea, and even death can occur if proper treatment is not implemented, (Gortner, Leupold, Pohlandt, & Bartmann, 1989; Harper, Healy, & Dennis, 1990; Kolodny & Yatziv, 1985; Naylor, 1985; Nord, van Doorninck, & Greene, 1991; McMahon & MacDonnell, 1989; Potashnik, Carmi, Sofer sofer
In Judaism, a scholar-teacher of the 5th–2nd centuries BC who transcribed, edited, and interpreted the Bible. The first sofer was Ezra, who, with his disciples, initiated a tradition of rabbinical scholarship that is still central in , Bashan, & Abeliovich, 1987; Tharp, 1992; Uziel, Savoiardo, & Nardoccii, 1988; Wendel, Langenbeck, & Seakins, 1989).
The characteristic odor, described as sweet, caramel-like, or similar to maple syrup, usually appears as neurological signs become evident (Harper, et al., 1990; Nord, van Doorninck, & Greene, 1991). The odor may be observed in the perspiration, ear ceriman, and in the urine. The smell is so strong that it is readily noticeable when one enters a room (Brismar, Aqeel, Brismar, Coates, Gascon, & Ozand, 1990).
Currently, the five recognized clinical forms of MSUD are classic, intermittent, intermediate, thiamine-responsive, and immunologic classifications (Fukutomi, Kitamura, Kawachi, Tsuji, Hashimoto, and Yoshioka, 1993; Danner & Elsas, 1989).
In classic MSUD the three essential amino acids (leucine, isoleucine, and valine), sometimes referred to as Brach-Chain Amino Acids (BCAA BCAA Branched Chain Amino Acid
BCAA British Columbia Automobile Association
BCAA Branched Chained Amino Acids
BCAA Boulder County Arts Alliance (Boulder, CO)
BCAA British Columbia Assessment Authority ), accumulate within the body, in addition to their respective keto acids, because of an inborn error in metabolism which results in profound effects on neurobological tissue (Westall, Dancis, & Miller, 1957). According to Danner and Elsas (1989), characteristics of this form of MSUD are sudden apnea, coma, and even death during the neonatal period, poor feeding, lethargy, and recurrent keto-acidosis during infancy. The newborn is normal until about 4 to 7 days of age. Poor feeding with a bottle, or nipple refusal, and sleepiness are usually first indicators. Breathing difficulties and central nervous system depression, leading to coma, may quickly follow and persist until BCKA concentrations are decreased (Danner & Elsas, 1989). Sweet smelling urine is not always present during the neonatal period, but is present in earwax earwax /ear·wax/ (er´waks) cerumen.
A waxlike secretion of certain glands lining the canal of the external ear; cerumen.
see cerumen. by 2 months of age (Danner & Elsas, 1989).
According to several sources, EEG EEG: see electroencephalography. abnormalities, severe psychomotor retardation, generalized dystonic posturing, and other evidences of structural brain dysfunctions are present if an untreated patient survives the first weeks of life. Bilateral ptosis Ptosis Definition
Ptosis is the term used for a drooping upper eyelid. Ptosis, also called blepharoptosis, can affect one or both eyes.
The eyelids serve to protect and lubricate the outer eye. , opthalmoplegia, and facial deplegia are common (Zee, Freeman, and Holtzman, 1974; MacDonald & Sher, 1977; Chhabria, Tomasi, & Wong, 1979; Haymond, Karl, Feigin, Devivo, & Pagliara, 1973). Moderate to severe hypoglycemia hypoglycemia: see diabetes.
Below-normal levels of blood glucose, quickly reversed by administration of oral or intravenous glucose. Even brief episodes can produce severe brain dysfunction. and hypoalaninamia also are present (Elsas, Priest, Wheeler, Danner, & Pask, 1974; Haymond, Ben-Galim, & Strobel, 1978; Lonsdale, Mercer, & Faulkner, 1963).
Usually the postnatal course in intermittent MSUD is uneventful. First indications of intermittent MSUD are seen between 2 months and 40 years of age (Danner & Elsas, 1989). These are triggered by otitis otitis
Inflammation of the ear. Otitis externa is dermatitis, usually bacterial, of the auditory canal and sometimes the external ear. It can cause a foul discharge, pain, fever, and sporadic deafness. , an upper respiratory tract infection upper respiratory tract infection URI Infectious disease A nonspecific term used to describe acute infections involving the nose, paranasal sinuses, pharynx, and larynx, the prototypic URI is the common cold; flu/influenza is a systemic illness involving the URT , immunization, an operation, or sudden increase in dietary protein (Pueschel, Bresnan, Shih, & Levy, 1979). An individual becomes irritable, ataxic a·tax·ic or a·tac·tic
Of, relating to, or characterized by ataxia. , and progressively lethargic. For a period of time the individual has a series of episodes with recovery concomitant with an elevation of BCAAs and BCKAs in blood and urine. During these episodes the maple syrup odor is noted (Duran, Tielens, Wadman, Stigter, & Kleijer, 1978; Kodama, Seki, Hanabusa, Morista, Sakurai, & Matsuo, 1976).
In 1970, Schulman, Lustberg, Kennedy, Museles, and Seegmiller described intermediate MSUD. In this subclass In programming, to add custom processing to an existing function or subroutine by hooking into the routine at a predefined point and adding additional lines of code.
subclass - derived class the postnatal period is normal, except for substaritial delays in developmental milestones (Van Der Horst & Wadman, 1971).
Individuals with intermediate MSUD have consistently high levels of BCAA and BCKA in blood and urine. Moderate anemia, high levels of uric acid in the blood, and mild systemic acidosis acidosis /ac·i·do·sis/ (as?i-do´sis)
1. the accumulation of acid and hydrogen ions or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, decreasing the pH.
2. are present (Schulman, Lustberg, Kennedy, Museles, & Seegmiller, 1970). By restricting dietary protein to 1.5 g/kg per day, concentrations of BCAAs and BCKAs in blood and urine can be lowered to normal.
Scriver, Mackenzie, Clow, and Deluin (1971) described the first thiamine-responsive individual with MSUD as having delayed neurological development. They reported plasma leucine concentrations normalized when both 10 mg/day thiamine and a simultaneous protein-restricted diet were followed. Scriver, Clow, & George, (1985) reported while following this same individual for 15 years, she had only five episodes of metabolic decompensation decompensation /de·com·pen·sa·tion/ (de?kom-pen-sa´shun)
1. inability of the heart to maintain adequate circulation, marked by dyspnea, venous engorgement, and edema.
2. . All five episodes were triggered by infections and other illnesses. Outside of two of these episodes, resulting in seizures and a coma, the girl led a normal life. Three weeks were required as a minimum time before responses could be observed; restricted dietary BCAAs program should be continued. Several other studies also reported biochemical mechanisms for thiamine response (Elsas & Danner, 1982; Danner, Lemmon, & Elsas, 1980; Danner & Priest, 1983; Elsas, et al., 1974; Van Der Horst & Wadma, 1971: Elsas & Danner, 1976; Fernhoff, Lubitz, Danner, Dembure, Schwartz, Hillman, Bier bier
1. A stand on which a corpse or a coffin containing a corpse is placed before burial.
2. A coffin along with its stand: followed the bier to the cemetery. , and Elsas, 1985).
Immunologic Classification MSUD
Polyclonal antibodies specific for BCKD proteins have been used to define mutations resulting in MSUD with immunologically altered proteins (Danner & Elsas, 1989). Two different studies defined two different antigen negative mutations referred to as E1B deficiency and E2 deficiency (Danner, Armstrong, Heffeifinger, Sewell, Priest, & Elsas, 1985; Indo, Kitano, Endo, Akaboshi, & Matsuda, 1987). These mutations had characteristics similar to classic MSUD (Danner et al., 1985: Indo, Kitano, Endo, Akaboshi, & Matsuda, 1987; Elsas et al., 1974; Duran & Wadman, 1985). Antibodies specific for E3 had been used to define individuals with antigenically present but catalytically inactive E3. These individuals had combined lactic and branched chain ketoaciduria branched chain ketoaciduria
See maple syrup urine disease. (Matuda, Kitano, Sakaguchi, Yoshino, & Saheki, 1981; Otulakowski, Nyhan, Sweetman, & Robinson, 1985; Robinson, Taylor, & Sherwood, 1977; Taylor, Robinson, & Sherwood, 1978; Robinson, Taylor, & Sherwood, 1980; Robinson, Taylor, Kahler, & Kirkman Kirk´man
n. 1. A clergyman or officer in a kirk.
2. A member of the Church of Scotland, as distinguished from a member of another communion. , 1981).
In 1963, Rubinstein and Taybi described a new syndrome which had characteristics of "broad short terminal phalanges phalanges
plural of phalanx. of the thumbs and great toes, with or without angulation angulation /an·gu·la·tion/ (ang?gu-la´shun)
1. formation of a sharp obstructive bend, as in the intestine, ureter, or similar tubes.
2. deviation from a straight line, as in a badly set bone. deformity; characteristic facial appearance with beaked or straight nose, antimongoloid slant of eye lid openings with apparent abnormal width between the eyes and grimacing smile, height and head circumference below 50th percentile; mental, motor, social, and language retardation; stiff awkward gait; and incomplete or delayed descent of testes in males" (Rubinstein, 1990). Since then some 300 publications on more than 600 patients in 40 countries have been written on Rubinstein-Taybi syndrome (RTS (Request To Send) An RS-232 signal sent from the transmitting station to the receiving station requesting permission to transmit. Contrast with CTS.
1. (operating system) RTS - run-time system.
2. ) or Broad Thumb-Hallux Syndrome (Hennekam, 1991; Rubinstein, 1990). Forty- six percent of patients were female and 54% male, with 14 black, 23 Japanese, 2 Chinese, with the rest Caucasian (Rubinstein, 1990). Twice as many cases have been reported in the United States as any other country, with Ohio and California having the most cases (Hennekam, et al., 1990.
RTS is considered to be very rare with an estimated incidence of one in 300,000 births, and a 1% chance of a couple having another child with RTS (Robinson, Stewart, & Hersh, 1993; Berry, 1987; Hennekam et al., 1990). Cause of the syndrome has not been completely established, but suspected to be an autosomal dominant mutation, either as a point mutation, or as a deletion at a submicroscopic submicroscopic /sub·mi·cro·scop·ic/ (-mi?kro-skop´ik) too small to be visible with the light microscope.
adj. level (Robinson, Stewart, & Hersh, 1993; Hennekam, 1991).
RTS was indicated during infancy by feeding difficulties, neonatal distress, recurrent respiratory infections, and gastrointestinal problems (Hennekam, Van Den Boogaard, Sibbles, & Van Spijker, 1990; Partington, 1990; Rubinstein, 1990). Appetite was often poor, and easy vomiting observed in most infants with RTS. These feeding problems were usually resolved spontaneously before the end of the first year (Hennekam et al., 1990). However, swallowing difficulties with easy choking might persist over the life span. Constipation is a frequent problem, necessitating medication and/or dietary regimes (Hennekam et al., 1990; Partington 1990; Rubinstein; 1990).
Rubinstein (1990) reported a variety of vocal abnormalities in RTS infants. These included stridor Stridor Definition
Stridor is a term used to describe noisy breathing in general, and to refer specifically to a high-pitched crowing sound associated with croup, respiratory infection, and airway obstruction. or hoarseness, low pitched or husky voices, a history of a weak whimper or abnormal cry, vocal cord paralysis Vocal Cord Paralysis Definition
Vocal cord paralysis is the inability to move the vocal cords and the resulting loss of vocal cord function.
Description , laryngospasm, or other abnormalities of the glottis glottis /glot·tis/ (glot´is) pl. glot´tides [Gr.] the vocal apparatus of the larynx, consisting of the true vocal cords and the opening between them.glot´tal
n. pl. . These vocal abnormalities might in part be resultant of pronounced facial changes in maxillary max·il·lar·y
Of or relating to a jaw or jawbone, especially the upper one.
A maxillar; a jawbone.
adj hypoplasia hypoplasia /hy·po·pla·sia/ (-pla´zhah) incomplete development or underdevelopment of an organ or tissue.hypoplas´tic
enamel hypoplasia , narrow palate, small jaw, and shape of the nose (Hennekam et al., 1990). This might also explain reports by several investigators, indicating articulation skills and spoken language were retarded (Lowry, 1990). Padfield, Partington, and Simpson (1968) indicated individuals who had learned to talk had distinct nasal quality.
Rubinstein (1990) and Partington (1990) reported stature and bone age were generally below the 50th percentile for age, and stature often below the fifth percentile. Rubinstein (1990) reported in individuals with RTS 18 years of age or older, both average and median adult heights were 61.5 inches for males and 58 inches for females; head circumference was below the 50th percentile, and microcephaly occurred in 94% of the cases (Rubinstein, 1990). Despite small sizes of heads, in 94% of cases, the anterior fontanel fontanel (fŏn`tənĕl'): see skull.
One of six soft spots at the junctions (sutures) of the cranial bones in an infant's skull, covered with tough, fibrous membrane. tended to be large or was late in closing in 29% of Rubinstein's (1990) cases.
The most characteristic facial abnormality found in all patients was the shape of the prominent and/or beaked nose, with or without a low nasal septum (Hennekam et al., 1990). Hennekam, Den Boogaard, Sibbles, and Van Spijker (1990) also reported downward-slanted palpebral fissures in 88% of their cases over 5 years of age, but in only 50% of cases below 5 years of age. Other facial abnormalities reported were heavy or highly arched eyebrows, a fold of skin extended from the root of the nose to the median end of the eyebrow, and minimal abnormalities in rotation, position, size, or shape of the ears. Because of positions of ears, conductive hearing losses might be of concern (Lowry, 1900).
The mouth appeared small, with dental irregularities and overcrowding overcrowding
overcrowding of animal accommodation. Many countries now publish codes of practice which define what the appropriate volumetric allowances should be for each species of animal when they are housed indoors. Breaches of these codes is overcrowding. in 67% of cases, but more commonly the upper lip appeared thin. A grimacing smile was reported in 76% of cases (Rubinstein, 1990).
A large variety of visual problems was reported for individuals with RTS. Whereas most reports emphasized abnormalities of the external eye, such as strabismus strabismus (strəbĭz`məs), inability of the eyes to focus together because of an imbalance in the muscles that control eye movement; also called squint. and abnormal distance between the eyes, some cases reported intraocular abnormalities. Iris abnormalities, cataracts, lens dislocation, glaucoma, lesion or defect of the retina, and dark brown, vascular coat of eye, and excavation of the optic disc interpreted as a glaucomatous cupping were all reported (Marcus-Harel, Silverstone, Seelenfreund, Schurr, & Berson, 1991; Rubinstein & Taybi, 1963; Legrand & Maurat, 1973; Roy, Summitt, Hiatt, & Hughes, 1978; Behrens-Baumann, 1977; Levy, 1976; Falbe-Hansen, 1969; Ziring, Weiss, & Cooper, 1974; Weber & Bernsmeier, 1983). Hennekam et al. (1990) reported 45% of all patients wore glasses for refraction refraction, in physics, deflection of a wave on passing obliquely from one transparent medium into a second medium in which its speed is different, as the passage of a light ray from air into glass. errors.
Retarded mental and motor development became apparent in the first year of life. According to Rubinstein (1990) 74% of individuals reported to have RTS had IQs under 50; however, Johnson (1966) and Rubinstein & Taybi (1963) both reported individuals' IQ's in the 80s on the Stanford-Binet test.
Developmental delays in motor skills were reported in almost all cases. Mazzone, Milana, Pratico, and Reitano (1989) and Robinson, Stewart, and Hersh (1993) indicated a 6-month delay in motor skills for RTS individuals. Hennekam, Van Den Boogaard, Sibbles, and Van Spijker (1990) reported mean age of rolling over was 9 months, sitting 15 months, standing 24 months, and walking 24 months for 30 cases of RTS. A number of physiological reasons were given for these motor delays. Hypotonia, lax ligaments, and hyper tensible joints were recorded in 70%; however, deep tendon reflexes were reported to be hyperactive in 53% of cases. Spina bifida, kyphosis kyphosis (kīfō`səs): see hunchback. , scoliosis Scoliosis Definition
Scoliosis is a side-to-side curvature of the spine.
When viewed from the rear, the spine usually appears perfectly straight. , and lordosis lordosis /lor·do·sis/ (lor-do´sis)
1. the anterior concavity in the curvature of the lumbar and cervical spine as viewed from the side.
2. abnormal increase in this curvature. were recorded in 63% of cases. Heart disease was reported in 34% of cases, and EEG abnormalities were reported in most all cases (Rubinstein, 1990; Hennekam et al., 1990; Mazzone, Milana, Pratico, & Reitano, 1989).
Abnormalities of glucose metabolism ranging from hypoglycemia to diabetes were reported by Rubinstein (1990). However, the main reason for several of these motor delays might be the result of club feet, webbing of the fingers, and congenital dislocation of the patella patella (pətĕl`ə): see kneecap. (Ramakrishnan, Sharma, Ramakrishnan, Parihar, Sharma, & Kanthu, 1990; Hennekam et al., 1990; Rubinstein, 1990; Moran, Calthorpe, McGoldrick, Fogarty, & Dowling, 1993; Jones, Fisher, & Curtis, 1976; Rubinstein & Taybi, 1963).
In Part I of this three-part series, the etiologies and indicators for individuals with Cornelia de Lange Syndrome, Maple Syrup Urine Disease, and Rubinstein-Taybi Syndrome were discussed. Though it is a common practice of educators to group individuals from all three of these syndromes into one group referred to as genetic disorders or to include them into the more generic classification of developmentally delayed, the reader should be able to see the needs of individuals from each of these syndromes are similar in a few cases, but often very different. Because of these differences, Part 2 of the series will discuss a few common techniques for teaching this group, while indicating teaching techniques need to be very different for most cases. In Part 3 of the series behavioral issues, suggestions for activities, and conclusions for teaching physical activity skills for those students with Cornelia de Lange Syndrome, Maple Syrup Urine Disease, or Rubinstein-Taybi Syndrome will be discussed.
Brismar, J., Aqeel, A., Brismar, G., Coates, R., Gascon, G., & Ozand, P. (1990). American Journal of Neuroradiology neuroradiology /neu·ro·ra·di·ol·o·gy/ (-ra?de-ol´ah-je) radiology of the nervous system.
1. The branch of radiology that deals with the nervous system. , 11, 1219-1228.
Brubacher, J. (1993). The big picnic. Maple Syrup Urine Disease Newsletter, 11, 4-5.
Cameron, T.H., & Kelly, D.P. (1988). Normal language skills and normal intelligence in a child with de Lange Syndrome. Journal of Speech and Hearing Disorders, 53, 219-222.
Chhabria,S., Tomasi, L.G., & Wong, P.W. (1979). Opbthalmopegia and bulbar palsy in variant form of Maple Syrup Urine Disease. Annuals of Neurology, 6, 71.
Cornelia de Lange Syndrome Foundation. (1994). Album. (Available from Cornelia de Lange Syndrome Foundation, 60 Dyer Avenue, Collinsville, CT 06022-1273).
Danner, D.J., & Elsas, L.J. (1989). Disorders of branched chain amino and keto acid metabolism. In Scriver, C.R., Beandet, A.L., Sly, W.S., & Valle, D. (Eds.). The metabolic basis of inherited disease (6th ed.) (pp 671-692). New York: McGraw-Hill.
Danner, D.J., & Priest, J.H. (1983). Branched chain ketoacid dehydrogenase activity and growth of normal and mutant human fibroblasts Fibroblasts
A type of cell found in connective tissue; produces collagen.
Mentioned in: Skin Grafting : The effect of branched chain amino acid concentration in culture medium. Biochemical Genetics, 21, 895.
Elsas, L.J., Priest, J.H., Wheeler, F.B., Danner, D.J., & Pask, B.A. (1974). Maple Syrup Urine Disease: Coenzyme coenzyme (kō-ĕn`zīm), any one of a group of relatively small organic molecules required for the catalytic function of certain enzymes. function and prenatal monitoring. Metabolism, 23, 569.
Filippe, G. (1989). The de Lange Syndrome: Report of 15 cases. Clinical Genetics, 35, 343-363.
Foster, R. (1989). Family center nursing care of children. Philadelphia, PA: W. B. Saunders Company.
Fukutomi, M., Kitamura, S., Kawachi, K.,Tsuji, T., Hashimoto, K., & Yoshioka, A. (1993). Successful repair and postoperative management of telrology of fallot in a patient with Maple Syrup Urine Disease. Heart and Vessels, 8, 48-51.
Goodban, M. T. (1993). Survey of speech and language skills with prognostic indicators in 116 patients with Cornelia de Lange Syndrome. American Journal of Medical Genetics, 47, 1059-1063.
Gortner, L., Leupold, D., Pohlandt, F., & Bartmann, P. (1989). Peritoneal dialysis in the treatment of metabolic crises caused by inherited disorders of organic and amino acid metabolism. Acta Paediatrics Scandinavian, 78, 706-711.
Halal, F., & Silver, K. (1992). Syndrome of micrucephaly, Brachmann de Lange-like facial changes severe metatarsus adductus, and developmental delay: Mil Brachmann-de Lange Syndrome. American Journal of Medical Genetics, 42, 381-386.
Harper, P.A., Healy, P.J., & Dennis, J.A. (1990). American Journal of Pathology, 136, (6), 1445-1447.
Hawley, S. P., Jackson, L. G., & Kurnit, D. M. (1985). Sixty-four patients with Brachmann-de Lange syndrome: A survey. American Journal of Medical Genetics, 20, 453-459.
Haymond, M.W., Ben-Galim, E. & Strobel, K.E. (1978). Glucose and alanine alanine (ăl`ənēn'), organic compound, one of the 20 amino acids commonly found in animal proteins. Only the l-stereoisomer participates in the biosynthesis of proteins (see stereochemistry). metabolism in children with Maple Syrup Urine Disease. Journal of Clinical Investigation The Journal of Clinical Investigation (JCI or J Clin Invest) is a leading biomedical journal, which is radically different from many of its peers in having a high impact factor (in 2006, 15.754) and offering all its contents entirely free. , 62, 398.
Haymond, M.W., Karl, I.E., Feigin, R.D., Devivo, D., & Pagliara, A.S. (1973). Hypoglycemia and Maple Syrup Urine Disease: Defective gluconeogenesis gluconeogenesis /glu·co·neo·gen·e·sis/ (gloo?ko-ne?o-jen´e-sis) the synthesis of glucose from molecules that are not carbohydrates, such as amino and fatty acids.
n. . Pediatric Research, 7, 500.
Jervis, A. G., & Stimson, C. W. (1963). De Lange Syndrome. The Amsterdam type mental defect with congenital malformations. Journal of Pediatrics, 63,634-645.
Kline, A. D., Barr, M., & Jackson, L.G. (1993). Growth manifestations in the de Lange Syndrome. American Journal of Medical Genetics Supplement, 47(7), 1042-1049.
Kolodny, E.H., & Yatziv, S. (1985). Laboratory approaches for inherited neurometabolic diseases. Developmental Medicine & Child Neurology, 27, 249260.
Lonsdale, D., Mercer, R.D., & Faulkner, W.R. (1963). Maple Syrup Urine Disease: Report of two cases. American Journal of Disease of Children, 106, 258.
MacDonald, J.T., & Sher, P.K. (1977). Ophthalmoplegia Ophthalmoplegia Definition
Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement. The condition can be caused by any of several neurologic disorders. as a sign of metabolic disease in the newborn. Neurology, 27, 970.
McMahon, Y., & MacDonnell Jr., R.C. (1990). Clearance of branched chain amino acids by peritoneal dialysis in Maple Syrup Urine Disease.
Meinecke, P., & Hayek, H. (1990). Brief historical note on the Brachmann de Lange Syndrome: A patient closely resembling the case described by Brachmann in 1916. American Journal of Medical Genetics, 35,449-450.
Menkes, J.H., Hurst, P.L., & Craig, J.M. (1954). A new syndrome: Progressive familial infantile cerebral dysfunction associated with an unusual urinary substance. Pediatrics, 14,462.
Menyuk, P. (1980). Effect of persistent otitis media on language development. Annals of Otology otology /otol·o·gy/ (o-tol´ah-je) the branch of medicine dealing with the ear, its anatomy, physiology, and pathology.otolog´ic
The branch of medicine that deals with the ear. Rhinology rhinology /rhi·nol·o·gy/ (ri-nol´ah-je) the medical specialty that deals with the nose and its diseases.
The anatomy, physiology, and pathology of the nose. , & Laryngology laryngology /lar·yn·gol·o·gy/ (-gol´ah-je) the branch of medicine dealing with the throat, pharynx, larynx, nasopharynx, and tracheobronchial tree.
n. , 68 (suppl) 257.
Mosher, G. A., Schulte, R. L., Kaplan, P. A., Buehler, B. A., & Sanger, W. G. (1985). Brief clinical report: Pregnancy in a woman with the Brachmann de Lange Syndrome. American Journal of Medical Genetics, 22, 103-107.
Motl, M. L., & Opitz, J. M. (1971). Studies of malformaton syndrome XXV A: Phenotypic and genetic studies of the Brachmann de Lange Syndrome. Human Heredity, 21, 1-16.
Naylor, E.W. (1985). Recent developments in neonatal screening. Seminars in Perinatology perinatology /peri·na·tol·o·gy/ (-na-tol´ah-je) the branch of medicine (obstetrics and pediatrics) dealing with the fetus and infant during the perinatal period.
n. , 9, (3), 232249.
Nord, A., van Doorninck, WJ., & Greene, C. (1991). Developmental profile of patients with Maple Syrup Urine Disease. Journal of Inherited Metabolic Diseases, 14, 881-889.
Northrup, H., Sigman, E.S., & Hebert, A.A. (1993). Exfoliative ex·fo·li·a·tive
Marked by exfoliation, desquamation, or profuse scaling. erythroderma resulting form inadequate intake of branched-chain amino acids The phrase branched-chain amino acids or BCAA is sometimes used to refer to the amino acids having aliphatic side-chains that are non-linear. These are leucine, isoleucine and valine. in infants with Maple Syrup Urine Disease. Archives Dermatology, 129, 384-385.
Opitz, J.M. (1985). Editorial comment: The Brachmann de Lange Syndrome. American Journal of Medical Genetics, 22, 89-102.
Potashnik, R., Carmi, R., Sorer, S. Bashan, N., & Abeliovich, D. (1987). Maple Syrup Urine Disease in a Bedouin tribe: Prenatal and postnatal diagnosis. Israel Journal of Medical Sciences, 23, 886-889.
Ptacek, L.J., Opitz, J.M., Smith, D.W., Gerritsen, T., & Waisman, H.A. (1963). The Cornelia de Lange Syndrome. Journal of Pediatrics, 63, 1000-1020.
Ramakrishnan, S., Sharma, D. C., Ramakrishnan, V., Parihar, P.S., Sharma, S., & Kanther, D. K. (1990). Rubinstein-Taybi syndrome. Indian Pediatrics, 27, 404-405.
Sataloff, R T., Spiegal, J.R., Hawkshaw, M., Epstein, J.M., & Jackson, L. (1990). Cornelia de Lange Syndrome: Otolaryngolgic manifestations. Archives of Otolaryngology Head & Neck Surgery, 116, 1044-1046.
Schlesinger, B., Clayton, B., Bodian, M., & Jones, K.V. (1963). Typus degenerative Amstelodamensis. Archives of Diseases in Childhood, 38, 349-357.
Snyderman, S.E., Norton, P.M., Roitman, E., & Holt, L.E. (1964). Maple Syrup Urine Disease with particular reference to dietotherapy. Pediatrics, 34,454.
Subramanyam, S.B., Qadri, S.M., Dhalla, M.B., & Ozand, P.T. (1990). The diagnosis and management of MSUD in Saudi Arabia by using two different methods. Indian Journal of Pediatrics, 57, 717-721.
Tharp, B.R. (1992). Unique EEG pattern (womblike rhythm) in neonatal Maple Syrup Urine Disease. Pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children.
Of or relating to pediatrics. Neurology, 8 (1), 65-68. U.S. 101st Congress: Public Law 101-476, October 30, 1990.
Uziel, G., Savoiardo, M., & Nardocci, N. (1988). CT and MRI CT and MRI
Two high technology methods of creating images of internal organs. Computerized axial tomography (CT or CAT) uses x rays, while magnetic resonance imaging (MRI) uses magnet fields and radio-frequency signals. Both construct images using a computer. in Maple Syrup Urine Disease. Neurology, 486-488.
Weber, U., & Bernsmeier, H. (1983). Rubinstein-Taybi syndrome and juveniles glaukom. Klin. Mbl. Augenkeilk, 183, 47.
Wendel, U., Langenbeck, U., & Seakins, J. (1989). Interrelation between the metabolism of Lisoleucine and L-allo-isoleucine in patients with Maple Syrup Urine Disease. International Pediatric Research Foundation, 25 (1), 1114.
Westall, R.G., Dancis, J., & Miller, S. (1957). Maple Sugar Urine Disease. American Journal of Diseases of Children, 94, 571-572.
Zee, D.S D.S Drainage Structure (flood protection) ., Freeman, J.M., & Holtzman, N.A. (1974). Ophthalmoplegia in Maple Syrup Urine Disease. Journal of Pediatrics, 84, 113.
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