Sacral Dimple Research Articles

Prenatal phenotype of 48, XXYY with elevated MSAFP

Elevated maternal serum alpha-fetoprotein (MSAFP) has long been associated with fetal abnormalities such as open neural tube defects, ventral wall defects, and cystic hygromas. The need for amniocentesis following a normal ultrasound has been debated because variability in ultrasound quality is vast. From several studies the incidence of fetal aneuploidy ranges from 0.6-1%, the incidence of all chromosomal abnormalities in women age 36 undergoing amniocentesis. We believe that providers should offer amniocentesis to women who have elevated MSAFP and a normal ultrasound since the quality of ultrasound varies widely.SD a G2 P1001, 32 year old Guyanese female, was seen for genetic counseling and amniocentesis at 19 weeks for elevated MSAFP (3.19MoM). Ultrasound performed a few days prior did not note any fetal abnormalities. Family history revealed the patient's brother had isolated polydactyly, a common malformation. She declined the procedure because of the risk of a miscarriage. An anatomic exam at 21 weeks revealed bilateral clubfeet and possible left-hand postaxial polydactyly. The patient declined amniocentesis again and missed an appointment for fetal echocardiography.The baby was born premature, at 29 weeks gestation by cesarian section. This was the second child born to these non-consanguineous parents. Birth weight was 1155 gms (25th%ile), length 37.5 cm (25th-50th%ile), and head circumference was 27.5 cm (50th - 75th%ile). Physical exam revealed minimal facial dysmorphic features including: hypertrichosis-especially of the forehead, relatively small eyes, lowset ears with malformed pinnae, and a prominent nasal bridge. Other notable findings included: normal male genitalia (with slight chordee), sacral dimple, long slender fingers, prominent convex nails and bilateral clubfeet (equinus varus). Chromosomal testing revealed a 48 XXYY karyotype, which may have originated from consecutive meiotic non-dysjunction during paternal gametogenesis.

Atypical Down Syndrome phenotype with translocation Trisomy 21

Down Syndrome (DS) is the most common chromosomal aneuploidy. Ninety-five percent of DS cases are due to free Trisomy while 3-4% are due to an unbalanced translocation. Generally, there are no phenotypic differences between these two causes of DS. We report an infant with Trisomy 21 due to 21q 21q translocation, who presented with an atypical DS phenotype.The proband was an AGA 36-week gestation infant born by SVD to a 35y.o. G2P2AB1 woman following two normal prenatal ultrasounds and a normal MSAFP. Pregnancy, labor and delivery were uncomplicated. At 2.5 months, exam revealed ht at 10-25th %, wt and HC at <5th%, mild facial asymmetry, high mildly deviated nasal bridge, downslanting palpebral fissures, absent Brushfield spots, moderate micrognathia, left ptosis, low set ears with overfolded superior helices, right Bell's palsy, left torticollis. Other findings were dermatoglyphics: right WRWAU, left ARUUU, tapered fingers with positional clenching of fist, sacral dimple and neurological abnormalities of hypertonia and arching of the back. Vision, hearing and echocardiogram were normal. By diagnostic criteria published in the J. of Peds. (1982), she did not meet the diagnosis of DS. Chromosome analysis by two laboratories at band level KI 550 revealed: 46,XX, +21, der (21; 21)(q10; q10). Both parents had normal karyotypes. FISH analysis utilizing the TUPLE; LSI 13,21 probe confirmed the Trisomy 21 translocation. At 8 months, she has continued hypertonia and developmental delay with functioning at 5-6 months.Our patient with Trisomy 21 due to translocation does not have the characteristic phenotype of DS. In 1977, Avramopoulos et al (1997) reported a patient with full standard Trisomy 21, who also had atypical phenotypes for DS. Possible etiologies for these findings may include: 1) small molecular deletion of the critical region of chromosome 21, 2) disruption of a gene by gene- gene interaction or 3) mosaicism in other cell lines. Further molecular research studies are planned.

Prenatal Diagnosis of dup(3q) syndrome

There are numerous reports on the duplication of the long arm of chromosome 3, ranging from 3ql2 to 3qter. Although the duplicated segments vary in size, a defined clinical phenotype, dup(3q) syndrome, has been investigated by us and others. A 22 year old G4P0030 (1SPAB, 2ELAB) Caucasian was referred at 31 weeks gestation for fetal anomalies on sonogram including hydrocephalus, bilateral polydactyly, and a possible CHD Amniocentesis was performed and showed an unbalanced chromosomal rearrangement: 46,XX,der(9)t(3;9) (q26.1;p24).ish. 46,XX,der(9)t(3;9)(q26.1;p24) (WCP3+WCP9+), and a positive acetylcholinesterase. Parental chromosomes showed that the father was a carrier of a balanced rearrangement: 46,XY,t(3;9) (q26.1;p24). The baby was bom at 42 weeks gestation following prostaglandin induction due to failure to progress. She weighed 4264 grains and cried spontaneously with APGAR scores of 8/8 at 1 and 5 minutes. The major dysmorphic features included: up-slanting palpebral fissures, synophyrs, prominent alveolar ridge, hypertelorism, down-turned corners of the mouth, short neck with redundant skin folds, bilateral postaxial polydactyly, a deep sacral dimple and an anteriorly displaced anus with low rectal stenosis. During the surgical correction of the rectal stenosis, a pre-sacral teratoma was excised. The telomeric DNA segment (9p24-pter) lost due to the translocation is generally associated with chromosomal capping rather than phenotypic expression. The clinical manifestations consistent with dup(3q) syndrome are being presented. To our knowledge, teratoma has not been described before as part of the dup3q phenotype.

Lumbosacral skin markers and identification of occult spinal dysraphism in neonates

Some skin lesions over the spine are known to be associated with occult spinal dysraphism, but the significance of common skin lesions, such as sacral pits and dimples, is uncertain. In this prospective study, 95 neonates (1.9% of 4989 live births) were referred with possible markers of occult spinal dysraphism. Seven of 94 babies examined had abnormalities demonstrated by spinal ultrasound, compared with 5 of 105 controls. In 2 of 94 and 3 of 105 of these, the conus medullaris was located at L3 but no other abnormalities were found. Of the 75 babies with a sacral dimple or pit alone, none had an abnormality, suggesting that these skin lesions do not indicate a high risk of occult spinal dysraphism.

The Wolf‐Hirschhorn syndrome in fetuses

Wolf-Hirschhorn syndrome (WHS) with partial deletion of the short arm of chromosome 4 has been exceptionally diagnosed in fetuses. We report prenatal diagnosis of five cases of monosomy 4p. The fetuses were karyotyped for severe intrauterine growth retardation (IUGR) diagnosed on routine ultrasound (US). In addition, cleft-lip and palate and diaphragmatic hernia respectively were found in two cases. The quantity of amniotic fluid was normal in all cases. At autopsy, the fetuses showed the typical craniofacial dysmorphy but without microcephaly. Major renal hypoplasia was the only constant visceral anomaly. Midline fusion defects were observed in all the fetuses, ranging from minor abnormalities such as scalp defect, hypertelorism, pulmonary isomerism, common mesentery, hypospadias and sacral dimple, to cleft palate, corpus callosum agenesis, ventricular septal defect, and diaphragmatic hernia. On post-mortem X-rays, a delayed bone age was always observed. All the placentae were hypotrophic, and two exhibited vascular lesions, although there was no maternal hypertension. Chromosomal studies showed that the breakpoints were within the 4p16 band in three cases, the 4p15 band in one case, and the 4p14 band in one case. The deletion was de novo in four cases, and resulted from a paternal translocation in one case. This study emphasizes the importance of karyotyping all fetuses with IUGR, especially when the quantity of amniotic fluid is normal, and suggests the possibility of recognizing on US the particular phenotype of WHS in utero.

Congenital Ocular Fibrosis With Musculoskeletal Abnormality: A New Association

Two siblings demonstrated an association of congenital ocular fibrosis (COF) syndrome with musculoskeletal abnormalities consisting of generalized muscle wasting, scoliosis, pigeon-chest deformity, bilateral fusion of the ribs in triplets, prominent coccyx, and sacral dimple. While most of the ocular and systemic "associations" hitherto described in the literature might have been coincidental, the coexistence of a generalized musculloskeletal disease with the COF syndrome raises the possibility that the ocular condition may be part of a more widespread disease process affecting the skeletal muscles.

Interstitial tandem direct duplication of the long arm of chromosome 4 (q23‐q27) and possible assignment of the structural gene encoding human aspartylglucosaminidase to this segment

We report on a girl with a previously undescribed de novo direct tandem duplication 4q involving the segment q23----q27. Clinical manifestations included postnatal growth and psychomotor retardation, microcephaly, hirsute forehead, epicanthic folds, strabismus, depressed nasal bridge, long philtrum, small mouth, tetralogy of Fallot, and sacral dimple. Her phenotype is compared with that of previously reported cases of duplication 4q. An increased activity of the enzyme aspartylglucosaminidase (AGA) in cultured fibroblasts was demonstrated. This suggests possible assignment of the AGA gene to the chromosomal segment 4q23----4q27.

Radiographic Manifestations of Congenital Anomalies of the Spine

Although the foregoing review of embryologic development and congenital anomalies of the spine in infants and children is necessarily brief, the most commonly encountered abnormalities have been reviewed, and when possible, an attempt has been made to cite the stage of embryologic development at which the various abnormalities originate. As noted, congenital abnormalities of the spine are relatively uncommon but may be of profound clinical significance. During the past decade, the most significant developments in the diagnosis and treatment of these abnormalities have been ultrasonography, CT scanning, and MR imaging. In the neonate, the spinal cord and neural outflow can be evaluated by ultrasonography until the osseous elements begin to fuse. Thereafter, MR imaging is the procedure of choice because it permits evaluation of the spine and spinal cord in all planes of imaging and provides detailed evaluation of the effect of osseous abnormalities on neural structures. Finally, plain radiographs of the spine for evaluation of neonates who have any of a spectrum of sacral dimples are rarely helpful, and in the presence of significant cutaneous or subcutaneous abnormalities, ultrasonography is the preferred modality for evaluation.

Association of congenital heart disease, blepharoptosis, and short stature.

We found 12 patients with congenital heart disease of unknown etiology complicated with blepharoptosis during a period from Sept. 1, 1981 to April 30, 1989. All the patients with congenital heart disease were acyanotic, including 10 with short stature. Among these 10, abnormalities of high frequency were intrauterine growth retardation (5 cases), mental retardation (5), microcephaly (3), epicanthus (4), high arched palate (4), sacral dimple (4), and distal axial triradius (3). It is postulated that the association of congenital heart disease, blepharoptosis and short stature might indicate pathogenetic relationships.

Sacrococcygeal lesions in children

Lesions in the sacrococcygeal region in children are mainly: (i) those associated with spina bifida- nearly always malformations: (ii) those without spina bifida—nearly all neoplasms. By far the commonest malformations are myelomeningoceles (190 cases in 35 years) and meningoceles (30 cases). These are followed by lipomas and lipomeningoceles (25) and dermoid cysts (13), both of which may be extraspinal or intraspinal or combined lesions. Both may be associated with a dermal pit, sinus or track from the skin to the spinal cord, which may tether the cord at a low level. There were 2 examples of a previously unreported malformation termed <i>pacinioma</i>. Each was in the form of a thick band running from a sacral dimple through an occult spina bifida to the spinal dura. They were composed purely of very well differentiated pacinian corpuscles, bearing no resemblance to myxoid (‘pacinian') neurofibromas. The neoplasms were mostly teratomas (54 cases) and these may rarely co-exist with spina bifida/ myelomeningocele. The purely post-sacral teratomas were benign and the dumb-bell and presacral tumours were often malignant. Ependymomas of the cauda equina (3) occasionally invade the sacrum and present as pre- or post-sacral masses. One rare purely subcutaneous ependymoma was resected from the natal cleft of a 4-yr-old girl. The coccyx was not removed and there has been no recurrence in 14 years. These are thought to arise from subcutaneous vestiges of the embryonic neural tube. Such vestiges were found in 10/15 control post-coccygeal regions from necropsies on infants aged 1 day to 1 year. No sacrococcygeal chordomas were seen.

Sacrococcygeal paciniomas

Two well differentiated pure Paciniomas, bearing no resemblance to neurofibromas, were resected from infants with spinal deformities. Each was in the form of a thick cord running from a sacral dimple through a low occult spina bifida to the spinal dura. The lesions are considered to be a malformation or hamartomatous overgrowth. Control sacrococcygeal regions from necropsies on 15 infants were examined histologically, and Pacinian corpuscles were found in 7, usually near the tip of the coccyx, and never numerous.

Trisomy for the distal third of the long arm of chromosome 19 in brother and sister

Trisomy for the distal third of the long arm of chromosome 19 was observed in a 12-year-old boy and his 9-year-old sister. Both are affected by extremely severe statural and psychomotor retardation. The physical symptoms common to both are dwarfism, micro- and brachycephaly, antimongoloid slant of the eyes, hypertelorism, ptosis, short nose, short philtrum, poorly formed ears, short neck with excess skin, barrel-shaped thorax, diastasis of rectus muscles, kyphosis, sacral dimple, excess of digital arches, pedes valgi, laterally curved big toes, epilepsy and muscular hypotonia. The chromosomal anomaly was transmitted by the mother, who is the carrier of a translocation t(19;20)(19q133;20pter). In the pedigree, extending over four generations, among 30 pregnancies fathered or mothered by 5 carriers resulted in: 6 individuals with normal karyotype, 9 carriers, 2 confirmed and 2 presumptive unbalanced abnormal children, and 10 abortions.

Multiple congenital anomalies/mental retardation (MCA/MR) syndrome due to partial 1q duplication and possible 18p deletion: A study of four individuals in two families

We have evaluated four individuals from two unrelated families with a similar multiple congenital anomalies/mental retardation (MCA/MR) syndrome due to partial duplication of chromosome 1q and possible deletion 18p. In both families the mothers and several relatives were carriers of the balanced translocation rcp t(1;18) (q42;p11). The features which the four have in common are relative macrocephaly, prominent forehead, micrognathia, and highly arched palate; three of the four individuals have short stature, scoliosis, kyphosis, hirsutism, camptodactyly, sacral dimple, repaired inguinal hernias, and eye abnormalities. Reproductive histories of five balanced translocation carriers in these families indicate that they have a high risk of spontaneous abortions and infants with multiple malformations.

A rare type of low birthweight dwarfism: The Dubowitz syndrome

Two patients with the Dubowitz syndrome are presented. This presumably recessive inherited syndrome was first defined by Grosse et al. (1971). So far 11 patients with this syndrome have been described. Major clinical findings are intrauterine and postnatal growth retardation, considerable microcephaly, mild mental retardation, hyperactivity, hyperextensibility of joints, eczema and a characteristic appearance of the face due to marked epicanthic folds, blepharophimosis, broadening of the bridge and tip of the nose and retrognathia. Minor anomalies as clinodactylyl of the firth digits, cutaneous syndactyly of toes, foot deformity, sacral dimple and cryptorchidism may be seen. The exclusion of the non genetic fetal alcohol syndrome presents serious diagnostic problems.

Partial deletion of the short arm of chromosome No. 4(4p-): Clinical studies in five unrelated patients

Five patients are described with a partial deletion of the short arm of a chromosome No. 4, which was identified autoradiographically. The 4p- syndrome can be distinguished from the cri du chat (5p-) syndrome by the absence of a catlike cry and the presence of a lower birth weight, more marked psychomotor retardation, a flat beaked nose with a fish-shaped mouth, seizures, cleft palate, coloboma of the iris, preauricular or sacral dimple or sinus, hypospadias, midline scalp defect, underdeveloped dermal ridges on palm and sole, lower finger ridge count, and delayed bone maturation.

PILONIDAL SINUS

The term pilonidal, derived from the Latinpilus, meaning hair, andnidus, meaning nest, was first applied to sinuses in the sacral region by Hodges1in 1880. However, the lesion was in all probability first described by J. W. Warren1in 1867. Since the first description of the lesion many terms have been suggested, such as coccygeal, sacrococcygeal or sacral sinus, dimple or fistula; postanal dimple, fistula or fissure; posterior umbilicus; postsacral or sequestration dermoid. From clinical usage the term pilonidal sinus has supplanted practically all of the other terms. At present the term pilonidal cyst or pilonidal sinus should be limited to those cysts or sinuses having their origin from the medullary canal, which should not be confused with the simple type of sacral dimple. The etiology of this interesting anomaly has been most intriguing to the majority of writers describing the sinus, as attested by the