Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 14-year-old boy was referred for a genetics evaluation after high-resolution chromosome analysis showed a small amount of extra material in the proximal long arm of chromosome 21. Five years prior, his karyotype analysis was interpreted as normal with a variant chromosome 21. The patient has short palpebral fissures, strabismus, flat antihelices of the ears, long thumbs with bilaterally absent interphalangeal creases, proximal bilateral 3/4 syndactyly, small testes, hypotonia, mental retardation, and speech problems. He has significant depression and behavioral problems including hyperactivity, aggression, and impulsivity. His 8-year-old brother has more severe behavioral disturbances and depression, but less significant mental retardation. A paternal aunt has mental retardation, is unusually docile, and appears similar to our patient. Chromosome analysis and fluorescence in situ hybridization (FISH) whole chromosome paint of chromosome 21 showed that the patient's father carries a "cryptic" balanced translocation, 46,XY, t(14;21)(q11.2;q11.2), as does the patient's paternal grandmother. Uniparental disomy studies using seven informative polymorphic nucleotide repeat markers from 14q and 21q confirmed biparental inheritance of the number 14 and 21 chromosomes for each brother, and indicate that they and the paternal aunt, all of whom inherited the der(14), are monosomic for proximal 21q and trisomic for proximal 14q. These karyotypes arose through an adjacent-2 segregation in the father on two occasions, and from the paternal grandmother on one occasion. This family is an example of recurrent malsegregation with translocations involving the acrocentrics.
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PMID:Recurrent adjacent-2 segregation of a familial t(14;21)(q11.2;q11.2): phenotypic comparison of two brothers and a paternal aunt inheriting the der(14). 1555 40

Partial monosomy of the q2 region of chromosome 15 has been infrequently reported. Moreover, interstitial deletions involving 15q22-q24 have been described in only nine patients to date. The phenotype of these reported individuals is subject to the extent of the deletion but typically includes altered muscle tone and significant developmental delays. In addition, eye abnormalities, such as strabismus, microphthalmia, or colobomas, ear abnormalities including cleft earlobe and preauricular tags, and urogenital defects are common features. Congenital heart defects, diaphragmatic hernia, abnormalities of the central nervous system, and skeletal anomalies have been reported but appear to be less frequent clinical manifestations. In this report, we describe three new patients with interstitial deletions involving 15q24, two with cryptic deletions identified by fluorescence in situ hybridization (FISH) with a probe for the PML gene and one with a cytogenetically visible deletion of 15q22.3-q24. The clinical presentation of these individuals is similar to those previously described and includes global developmental delays, hypotonia, and genital abnormalities in the males. The identification of these three cases demonstrates that the above clinical features are associated with a new cytogenetic deletion syndrome. Furthermore, we suggest that FISH analysis with a probe for the PML gene be performed in patients with these physical findings.
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PMID:A report of three patients with an interstitial deletion of chromosome 15q24. 1600 17

Many phenotypic manifestations have been reported in cardiofaciocutaneous (CFC) syndrome, but none, to date, are pathognomonic or obligatory. Previous histopathological studies reported findings in skin and hair; no autopsy studies have been published. We report the clinical and autopsy findings of a 7-year-old boy with severe CFC syndrome and malnutrition of psychosocial origin. Manifestations of CFC, reported previously, included macrocephaly and macrosomia at birth; short stature; hypotonia; global developmental delays; dry, sparse thin curly hair; sparse eyebrows and eyelashes; dilated cerebral ventricles; high cranial vault; bitemporal constriction; supraorbital ridge hypoplasia; hypertelorism; ptosis; exophthalmos; depressed nasal bridge; anteverted nostrils; low-set, posteriorly-rotated, large, thick ears; decayed, dysplastic teeth; strabismus; hyperelastic skin; wrinkled palms; keratosis pilaris atrophicans faciei; ulerythema ophryogenes; hyperkeratosis; gastroesophageal reflux; and tracheobronchomalacia. Additional findings, not previously reported, include islet cell hyperplasia, lymphoid depletion, thymic atrophy and congenital hypertrophy of peripheral nerves with onion bulb formations. Although the islet cell hyperplasia, lymphoid depletion, and thymic atrophy are nonspecific findings that may be associated with either CFC or malnutrition, the onion bulb hypertrophy is specific for a demyelinating-remyelinating neuropathy. These findings implicate congenital peripheral neuropathy in the pathogenesis of the developmental delays, feeding difficulties, respiratory difficulties, ptosis and short stature in this case. Additional studies of other cases of CFC are needed.
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PMID:Cardiofaciocutaneous syndrome (CFC) with congenital peripheral neuropathy and nonorganic malnutrition: an autopsy study. 1600 34

Two unrelated girls, aged 11 and 14 years, with clinical manifestations of Ehlers-Danlos syndrome (EDS) type VIB, characteristic facies, skeletal abnormalities, and other features are described. They had Marfanoid habitus with pectus excavatum; fragile, hyperextensible, and readily bruisable skin with widened, atrophic scars; recurrent hematomas; generalized joint laxity; hypotonia; scoliosis; and mild delay of gross motor development. Lysyl hydroxylase deficiency was ruled out in Patient 1. Parental consanguinity was present in Patient 2. They both had, in early childhood, down-slanting palpebral fissures, drooping lower eyelids, short nose, small mouth, and long philtrum. Facial features that persisted included thick eyebrows, hypertelorism, strabismus, blue sclerae, low-set, and slanted ears, hypoplastic columella, high-arched palate, and thin upper lip. They had tubular stenosis of the phalanges, metacarpals, and metatarsals; decreased physiological curvatures of the spinal column with tall vertebrae; and joint contractures including talipes equinovarus and progressive talipes valgus. Their hearing of high-pitched sounds was impaired. They had constipation and recurrent cystitis with an enlarged bladder. In view of these findings, we propose that these two girls represent a clinically recognizable subgroup of EDS type VIB.
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PMID:Ehlers-Danlos syndrome type VIB with characteristic facies, decreased curvatures of the spinal column, and joint contractures in two unrelated girls. 1615 41

In recent years, subtelomeric rearrangements have been identified as a major cause of multiple congenital anomalies/mental retardation syndromes. Currently, more than 2,500 individuals with mental retardation have been tested and reported in whom subtelomeric rearrangements were detected ranging from 2% to 29%. Therefore, subtelomeric FISH analysis is indicated as a second tier test after high-resolution G-banding analysis in patients with otherwise unexplained developmental delay/mental retardation and/or multiple congenital anomalies. We describe a patient and her three maternal female cousins, all showing an undiagnosed MCA/MR syndrome, associated with the same complex subtelomeric rearrangement. Subtelomeric FISH testing performed between 3(1/2) and 18 years after the initial karyotype showed, in all four patients, distal trisomy 3q and distal monosomy 10q as follows: 46,XX,ish der(10)t(3;10)(q29;q26.3)mat(D10S2488+,D10S2490-, D3S1272+,D10Z1+). Parental subtelomeric FISH analysis showed that the proposita's mother and three of four brothers and one of two sisters had a cryptic balanced 3:10 telomere translocation. The three brothers with the balanced translocation were father to one each of the three proband's cousins. All four affected girls showed a similar phenotype with pre/postnatal growth retardation, microcephaly, severe developmental delay/mental retardation, poor/absent speech, and a distinct pattern of malformation. On examination there were coarsening of facial features with low fronto-temporal hairline; thick eyebrows; bilateral epicanthal folds; hypertelorism; prominent nose with squared nasal root and narrow alar base; low-set posteriorly rotated large ears with a prominent anthelix; high arched palate; prominent chin; hands/feet brachydactyly; bilateral squint; hypotonia; and muscle hypotrophy. A slow overall improvement was seen in all patients over time. To our knowledge, this complex subtelomeric rearrangement in our patients has never been reported so far. Monosomy 10q has recently been described either isolated or as part of a complex rearrangement involving telomeres other than the 3q. Trisomy 3q29 has not yet been reported, but our patients resembled cases with 3q26 trisomy suggesting that the critical region of duplication for this phenotype is in 3q29.
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PMID:Familial complex 3q;10q rearrangement unraveled by subtelomeric FISH analysis. 1635 44

We describe two sisters with a mild-onset variant of Canavan's disease who presented at age 50 and 19 months with developmental delay but without macrocephaly, hypotonia, spasticity, or seizures. Remarkably, both patients had age-appropriate head control, gross motor development, and muscle tone. There were very mild deficits in fine motor skills, coordination, and gait. Both sisters had a history of strabismus, but otherwise vision was normal. The older child showed evidence of mild cognitive and social impairment, whereas language and behavior were normal for age in the infant. Both patients were found to be compound heterozygotes for C914A (A305E) and G212A (R71H) mutations in ASPA. Like all other known ASPA mutations, this previously unknown G212A mutation appears to have low absolute enzyme activity. Nevertheless, it is associated in these patients with an extremely benign phenotype that is highly atypical of Canavan's disease. Biochemical and clinical data were evaluated using a generalized linear mixed model generated from 25 other subjects with Canavan's disease. There were statistically significant differences in brain chemistry and clinical evaluations, supporting a distinct variant of Canavan's disease. Future studies of ASPA enzyme structure and gene regulation in these subjects could lead to a better understanding of Canavan's pathophysiology and improvements in ASPA gene therapy.
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PMID:Mild-onset presentation of Canavan's disease associated with novel G212A point mutation in aspartoacylase gene. 1643 72

Congenital hypothyroidism (CH) is the commonest treatable cause of mental retardation. The prevelance is 1/3000 - 1/4000 live births worldwide. The importance of CH is that, the longer the diagnosis of CH is delayed, the higher the risk of mental retardation and neurologic sequale; such as poor motor coordination, ataxia, spastic diplegia, muscular hypotonia, strabismus, learning disability and diminished attention span. The most common cause of permenant CH is thyroid dysgenesis (85-90%) in which the transcription factors TTF1,TTF2 and PAX8 would appear to be obvious candidate genes in the aetiology. Especially cardiac defects and some other birth defects are described in patients with CH. Inborn errors of thyroid hormonogenesis are responsible for 10-15% of CH cases and usually have autosomal recessive inheritance, consistent with a single gene mutation. Transient CH is very common in prematures with an estimate of 10% of CH babies identified on newborn screening, or 1 in 40,000 neonates. CH neonates are usually symptom-free and the most encountered symptoms are prolonged jaundice, large fontanelles and umbilical hernia. In general, the extent of clinical findings depends on the cause, severity and duration of hypothyroidism. An elevated TSH>20 microm Iu/L and a decreased concentration of T4 confirms the diagnosis of CH. Infants with permanant abnormalities of thyroid function mostly have a serum TSH concentration > 50 microm Iu/L. Ultrasonography, thyroid scintigraphy, bone x ray of the knee and serum thyroglobulin concentration are the other essentials after diagnosis to clarify the status of the thyroid and the severity of hypothyroidism. The higher doses of 10- 15 microm g/kg/day and the commencement of treatment before 2 weeks gave rise to better long term outcome of CH patients. In the follow up of the patients noncompliance is the most important problem and serum freeT4 or T4 and TSH should be obtained at each visit to adjust the doses of L-thyroxine. Still a small number of patients with severe hypothyroidism in utero or reflected by clinical signs and symptoms extremely low T4 levels and delayed bone age may have intellectual deficits despite normal intelligence.
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PMID:Congenital hypothyroidism clinical aspects and late consequences. 1644 57

A boy with chromosome 14 terminal (14q32.3) deletion presented with typical facial dysmorphism, mental retardation, and hypotonia. Ocular examination revealed esotropia, jerk nystagmus, microcornea, and retinal-choroidal colobomas. We report the first case of microcorneas and colobomas in association with chromosome 14 terminal deletion to help further define this clinical syndrome.
J Pediatr Ophthalmol Strabismus
PMID:Ocular manifestations of chromosome 14 terminal deletion. 1659 78

Interstitial deletions in the terminal region of chromosome 6 are rare. The deletion most often occurs de novo. Mental retardation is always described. The most characteristic manifestations are microcephaly, micrognathia, hypotonia, typical facial appearance, strabismus, and congenital heart defects. Although this chromosomal syndrome does not appear to have a distinctive phenotype, epileptic seizures are uncommon in affected individuals. We report on a novel finding in a patient with the 46 XX karyotype and del(6)(q25-q26) who developed intractable epilepsy.
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PMID:Deletion of the long arm of chromosome 6: report on a new case with intractable epilepsy. 1694 41

An 18-month-old boy presented with delayed milestones, hypotonia, strabismus and an episode of seizure. Magnetic resonance (MR) imaging of the brain revealed abnormally-oriented and thickened superior cerebellar peduncle, giving rise to the characteristic molar tooth sign on axial images. The isthmus was thinned out, with widened interpeduncular cistern and hypoplastic vermis. The clinical and MR imaging features were diagnostic of Joubert syndrome.
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PMID:Clinics in diagnostic imaging (118). 1772 72


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