| Coffin-Lowry syndrome
Síndrome de Coffin-Lowry
|José C.S. Guitti, Fabianne F. Peres|
|J Pediatr (Rio J) 2000;76(4):305-9|
Objective: To promote the diffusion of the knowledge on the Coffin-Lowry syndrome and to contribute to the outline of the disease. Methods: Case report.
Results: The clinical signs of a patient with the Coffin-Lowry syndrome are described and discussed.
Conclusions: The Coffin-Lowry syndrome, a X-linked genetic disease, is probably underdiagnosed in Brazil. The typical facies, dental-skeletal anomalies and mental retardation suggest the diagnosis, which can be clinically established by radiographic study of the hands.
Coffin et al. (
CLS is a well-established X-linked syndrome. Biancalana et al.4 confirmed
that the RSK2 gene - whose mutation originates the syndrome - is located
on the X chromosome. More recently, Schutz et al. (
Although carrier's facies is typical, it is likely that CLS has been underdiagnosed because clinicians may be inadequately trained to carry out dysmorphological examinations. Evidence of such possibility is that there is no reference to any publication in Latin America (Medline, Lilacs) except for two cases reported in Mexico ().
Physical examination: weight = 30 kg (25th-50th percentile); height = 117.5 cm (< 2.5th percentile), head circumference = 51 cm (50th percentile); blood pressure = 108 x 65; heart rate = 86 bpm. Protosystolic regurgitation murmur, grade II/VI, in tricuspid and mitral areas; systolic ejection murmur, grade II/VI, in pulmonary area, normal first sound; slightly louder second sound, with fixed unfolding. Clear lungs.
No visceral enlargement. No spinal anomalies. Normal, symmetric limbs.
Flat feet. Grotesque facies (Figure 1), with bitemporal narrowing, hypertelorism,
downward-slanting palpebral fissures, and thick eyelids. Broad-based nose
with a thick septum. Pouting everted lower lip; smooth tongue. Low-set
ears. Hypodontia (Figure 2). Thick and loose skin, velvety surface. Small
but puffy hands, short fingers, discrete thickening and absence of anomalous
hypothenar fold. Unstable, waddling broad-based gait. Reduced osteotendinous
reflexes. Right inguinal hernia surgical scar. Normal genitals. Apparently
normal hearing. Docile behavior with moments of irritability, utterance
of inarticulate sounds to show dissatisfaction.
Figure 1 -
Figure 2 -
Family history: Mother's height in the 10th-25th percentile. Normal aspect,
except for a slightly thickened septum, bilateral frontal prominence,
and bitemporal narrowing (Figure 3). Father with normal aspect. Maternal
grandparents, three uncles, seven aunts and two first-degree cousins reported
to have normal appearance. Paternal family reported to be normal (family
members were not studied as they live in another state).
Figure 3 -
Complementary investigation: Kariotype 46XY (cytogenetic analysis of metaphasic cells). Complete blood count and urinalysis: type I, normal. Chest radiography: no skeletal anomalies; signs of venous stasis in pulmonary circulation; slightly enlarged cardiac area with convex middle aortic arch. Normal spine radiography.
Radiography of lower limbs: short and wide femoral neck. Radiography of the skull and face: absence of frontal sinuses; thickened nasal septum and supraorbital ridge; multiple hypodontia. Radiography of the hands: tapering distal phalanges with tufting (Figure 4). Normal gastroesophageal reflux. Cranial CAT scan: slight cortical atrophy, with mild dilatation of the supratentorial ventricular system.
Electroencephalogram: diffuse irritative encephalic activity. Electrocardiogram: sinus rhythms; low-voltage QRS complexes, and diffuse change in ventricular repolarization. Echodoppler cardiogram: situs solitus; normal segmental analysis; slight enlargement of the four chambers; diffuse, insignificant involvement of the left ventricle; moderate insufficiency of the tricuspid and mitral valves; pressure on pulmonary artery = 69 mmHg; ejection fraction = 0.54; ostium secundum interarterial communication with a diameter of 0.4 cm (Figure 5). Hearing test was not performed.
Figure 4 -
Figure 5 -
The original descriptions of this syndrome by Coffin et al. (
Short stature becomes progressively apparent in childhood, although it
has already been observed as an early manifestation in a 5-month old infant
Other orodental findings have been described, such as high and narrow palate, malocclusion, and deep midline lingual furrow ().
Truncal anomalies include pectus excavatum or carinatum and spinal deformities.
Inguinal hernia, rectal and uterine prolapse have also been reported (
The alterations in the extremities are discreet but characteristic. The
hands are puffy, with short and hyperextensible fingers, with tapering
or fusiform tips. The fingernails may be markedly hyperconvex. Flat feet
and shortening of one of the lower limbs may occur and contribute to accentuate
the clumsy, waddling gait (
Osteocartilaginous involvement may affect the whole skeleton, and is
more severe when it affects vertebra and intervertebral disk (
Neurological manifestations also include skull base deformities and important
changes in the corpus callosum (
Crow et al (
Repeated pneumonia, probably secondary to problems in swallowing or gastroesophageal
reflux, was reported by Bustos Lozano et al. (
For infants with suggestive facies and developmental retardation, as
well as older children who are not thriving, the following differential
diagnosis should be considered: idiopathic hypercalcemia (William's syndrome),
embryopathy by hydantoin, trisomy 21, cretinism, mucopolysaccharidosis,
Soto's syndrome, fragile X syndrome, and, in adult patients, acromegaly
Genetic transmission occurred through the women in all families in which several generations where affected, and there is no evidence of male transmission up to the moment (). Hunter et al. ( ) studied 16 pedigrees, and only six had more than one person affected. All the others had only one carrier of this syndrome, which may be the result of de novo mutations. More recently, Jacquot et al. ( ) studied a family with four children where two were normal and two presented DNA mutations and CLS clinical features. The mother's lymphocyte DNA did not present signs of mutation.
These findings were consistent with the hypothesis of mutation occurring as a postzygotic event and configuring a germline mosaicism, which would make it impossible to offer conventional genetic counseling for this family and for similar cases. The same authors concluded that, for such reasons, the precise identification of the causing factor in all cases is of paramount importance.
|José C.S. Guitti - Professor, Department of Pediatrics at the Mother-Child and Community Health Department, Center for Health Sciences. Universidade Estadual de Londrina, Londrina, Paraná.|
|Fabianne F. Peres - Resident in Pediatrics. Hospital Universitário Regional do Norte do Paraná. Universidade Estadual de Londrina, Londrina, Paraná.|
|Top | Close|
Dr. José do Santos Guitti
Rua Paranaguá, 934 - 86020-030 - Londrina - PR
Fone: (43) 324.6095 - E-mail: firstname.lastname@example.org
|Title of the article: "Coffin-Lowry syndrome"|
|1. Coffin GS, Siris E, Wegienka LC. Mental retardation with osteocartilagenous anomalies. Am J Dis Child 1966; 112: 205-13.|
|2. Lowry B, Miller JR, Fraser FC. A new dominant gene mental retardation syndrome: association with small stature, tapering fingers, characteristic facies, and possible hydrocephalus. Am J Dis Child 1971; 121: 496-500.|
|3. Temtamy AS, Miller JD, Hussels-Maumenee I. The Coffin-Lowry syndrome: an inherited faciodigital mental retardation syndrome. J Pediat 1975; 86: 724-31.|
|4. Biancalana V, Trivier E, Weber C, Weissenbach J, Rowe PS, O’Riordan JL et al. Construction of a high-resolution linkage map for Xp22.1-p22.2 and refinement of the genetic localization of the Coffin-Lowry syndrome gene. Genomics 1994; 22: 617-25.|
|5. Schutz CK, Ives EJ, Chalifoux M, MacLaren L, Farrell S, Robinson PD et al. Regional localization of an X-linked mental retardation gene to Xp21.1-Xp22.13 (MRX38). Am J Med Genet 1996; 64: 89-96.|
|6. Jacquot S, Merienne K, De Cesare D, Pannetier S, Mandel JL, Sassone-Corsi P et al. Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations. Am J Human Genet 1998; 63: 1631-40.|
|7. Young ID. The Coffin-Lowry syndrome. J Med Genet 1988; 25: 344-48.|
|8. Barajas LO, Rivera H, Fragoso R, Nazara Z, Cantu JM. Síndrome Coffin-Lowry: descripción de dos casos. Bol Med Hosp Inf Mex 1986; 43: 378-81.|
|9. Wilson WG, Kelly TE. Early recognition of the Coffin-Lowry syndrome. Am J Med Genet 1981; 8: 215-20.|
|10. Hunter AGW, Partington MV, Evans JÁ. The Coffin-Lowry syndrome. Experience from four centres. Clin Genet 1982; 21: 321-35.|
|11. Salinas CF. Orodental findings and genetic disorders. Birth Defects 1982; 18: 79-120.|
|12. Kousseff BG. Coffin-Lowry syndrome in an Afro-American family. Am J Med Genet 1982; 11: 373-5.|
|13. Smith DW. Síndromes de malformações congênitas. 2a ed. São Paulo: Ed. Manole; 1997. p.273-4.|
|14. Procopis PG, Turner B. Mental retardation, abnormal fingers, and skeletal anomalies. Coffin’s syndrome. Am J Dis Child 1972; 124: 258.|
|15. Tokumaru AM, Barkovitch AJ, Ciricillo SF, Edwards MS. Skull base and calvarial deformities: association with intracranial changes in craniofacial syndromes. Am J Neuroradiol 1996; 17: 619-30.|
|16.Soekarman D, Fryns JP. Corpus callosum agenesis in Coffin-Lowry syndrome. Genetic Counseling 1994; 5: 77-80.|
|17. Sivagamasundari U, Fernando H, Jardine P, Rao JM, Lunt P, Jayewardene SL. The association between Coffin-Lowry syndrome and psychosis: a family study. J Intellec Disab Res 1994; 38: 469-73.|
|18. Crow YJ, Zuberi SM, McWilliam R, Tomie JL, Hollman A, Pohl K, et al. “Cataplexy” and muscle ultrasound abnormalities in Coffin-Lowry syndrome. J Med Genet 1998; 35: 94-8.|
|19. Bustos Lozano G, Barrionuevo Porras JL, Sanchez de Pozo J, Lledo G, Gallego M. Coffin-Lowry syndrome with repeated pneumonia. An Esp Pediat 1988; 28: 451-3.|
|20. Gorlin RJ, Brown D, Sauk J. Coffin-Lowry syndrome – a storage disorder? Birth Defects 1978; 14: 175.|
|21. Beck M, Glössl J, Rüter R, Kresse H. Abnormal proteodermatan sulfate in three patients with Coffin-Lowry syndrome. Pediat Res 1983; 17: 926-29.|
|22. Jacquot S, Merienne K, Pannetier S, Blumenfeld S, Schinzel A, Hanauer A. Germline mosaicism in Coffin-Lowry syndrome. Eur J Human Genet 1998; 6: 578-82.|
|Top | Close|
| Copyright Sociedade Brasileira de Pediatria © 2001 - All rights reserved
All services in this site are free. This is possible thanks to a donation given by Nestlé Infants Nutrition