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Neu-Laxova Syndrome
The Neu-Laxova syndrome is a lethal disorder character- ized by multiple congenital malformations. Microcephaly, lissencephaly, absence of corpus callosum, facial anomalies (notably absent eyelids), short broad neck, peripheral edema, ichthyosis, limb anomalies and other malformations are com- mon findings. The syndrome was described first by Neu et al.
in 1971 and Laxova et al. in 1972.
GENETICS/BASIC DEFECTS
1. Inheritance: autosomal recessive inheritance 2. Pathogenesis: unknown
CLINICAL FEATURES
1. Considerable intrafamilial and interfamilial variation in clinical features
2. Prenatal history
a. Severe intrauterine growth retardation b. Polyhydramnios
3. Spectrum of skin lesions
a. Edema over the dorsum of foot and hand, often asso- ciated with hypoplastic phalanges
b. Thick, waxy, and stretched in appearance
c. Peeling of skin, scaling, and extensive plaque forma- tion over scalp, face, neck, back, and arm
d. Translucent flexible membrane covering most of the skin
e. Varying degree of lamellar ichthyosis 4. Craniofacial features
a. Receding forehead b. Ocular hypertelorism
c. Exophthalmos (protruding eyes) d. Absence of the eyelids
e. Flat, abnormal nose f. Eclabium
g. Cataract h. Micrognathia
i. Cleft palate/lip j. Hypodontia
k. Low-set, malformed ears 5. CNS abnormalities
a. Microcephaly b. Lissencephaly
c. Hypoplastic or abnormal cerebellum
d. Agenesis or dysgenesis of the corpus callosum e. Decreased or absent gyri
f. Dilatation or abnormal ventricles g. Dandy-Walker malformation h. Choroid plexus cysts 6. Limb anomalies
a. Deformed digits b. Deformed limbs
c. Flexion deformity
d. Severe edema of the hands and feet e. Syndactyly
f. Rocker-bottom feet 7. Other features
a. Short broad neck b. Cystic hygroma c. Subcutaneous edema d. Small thorax
e. Hypoplastic or atelectatic lungs f. Small abdomen
g. Hypoplastic genitalia h. Short umbilical cord
i. Absence of hair j. Muscle atrophy
8. Classification proposed by Curry (1982): may represent heterogeneity of the condition or different grades of severity
a. Group I
i. Joint contractures ii. Partial syndactyly iii. Thin scaly skin
iv. Mild ichthyosis
v. Poor mineralization of bones b. Group II
i. Massive swelling of hands and feet ii. Ichthyosis
iii. Undermineralized bones c. Group III
i. Hypoplastic digits
ii. Severe ichthyosis (harlequin-like fetus) iii. Short limbs
iv. Stick-like long bones 9. Prognosis
a. Stillborn
b. Die shortly after birth
DIAGNOSTIC INVESTIGATIONS
1. Radiography
a. Multiple contractures b. Hemivertebrae c. Kyphoscoliosis 2. Histopathology of the skin
a. Hyperkeratosis
i. With or without parakeratosis
ii. Associated with abundant subcutaneous tissue and excess of fat
b. Myxomatous connective tissue associated with excess subcutaneous adipose tissue
c. Epidermal and dermal atrophy
3. Ultrasound of the brain for CNS anomalies 4. Normal chromosomes
NEU-LAXOVA SYNDROME 719
GENETIC COUNSELING
1. Recurrence risk a. Patient’s sib: 25%
b. Patient’s offspring: a lethal entity not surviving to reproductive age
2. Prenatal ultrasonography
a. Severe growth retardation: a major feature b. Polyhydramnios
c. Microcephaly/deficient calvarial ossification d. CNS abnormalities
e. Abnormal facies including receding forehead f. Exophthalmos
g. Cataract
h. Cystic hygromas i. Pulmonary hypoplasia j. Contractures
k. Excessive edema of the hands and feet l. Syndactyly
m. Clubbing of the feet
n. Absence of breathing movements, sucking, swallow- ing, or normal isolated arm and leg movements o. Restricted fetal movement
3. Management
a. No specific treatment for the uniformly lethal disorder b. Mainly supportive with initial management of venti-
latory, thermal, and nutritional support
REFERENCES
Abdel Meguid N, Temtamy SA: Neu Laxova syndrome in two Egyptian fami- lies. Am J Med Genet 41:30–31, 1991.
Aslan H, Gul A, Polat I, et al.: Prenatal diagnosis of Neu-Laxova syndrome: a case report. BMC Pregnancy Childbirth 2:1–4, 2002.
Curry CJ: Further comments on the Neu-Laxova syndrome. Am J Med Genet 13:441–444, 1982.
Driggers RW, Isbister S, McShane C, et al.: Early second trimester prenatal diagnosis of Neu-Laxova syndrome. Prenat Diagn 22:118–120, 2002.
Durr-e-Sabih, Khan AN, Sabih Z: Prenatal sonographic diagnosis of Neu- Laxova syndrome. J Clin Ultrasound 29:531–534, 2001.
Ejeckam GG, Wadhwa JK, Williams JP, et al.: Neu-Laxova syndrome: report of two cases. Pediatr Pathol 5:295–306, 1986.
Fitch N: Comments on Dr. Curry’s classification of the Neu-Laxova syndrome.
Am J Med Genet 15:515–517, 1983.
Fitch N, Resch L, Rochon L: The Neu-Laxova syndrome: comments on syn- drome identification. Am J Med Genet 13:445–452, 1982.
Gulmezoglu AM, Ekici E: Sonographic diagnosis of Neu-Laxova syndrome. J Clin Ultrasound 22:48–51, 1994.
Hickey P, Piantanida E, Lentz-Kapua S, et al.: Neu-Laxova syndrome: a case report. Pediatr Dermatol 20:25–27, 2003.
Hirota T, Hirota Y, Asagami C, et al.: A Japanese case of Neu-Laxova syn- drome. J Dermatol 25:163–166, 1998.
Horn D, Muller D, Thiele H, et al.: Extreme microcephaly, severe growth and mental retardation, flexion contractures, and ichthyotic skin in two broth- ers: a new syndrome or mild form of Neu-Laxova syndrome? Clin Dysmorphol 6:323–328, 1997.
Kainer F, Prechtl HF, Dudenhausen JW, et al.: Qualitative analysis of fetal movement patterns in the Neu-Laxova syndrome. Prenat Diagn 16:667–669, 1996.
King JAC, Gardner V, Chen H, et al.: Neu-Laxova syndrome: pathological eval- uation of a fetus and review of the literature. Pediatr Pathol Lab Med 15:57–79, 1995.
Laxova R, Ohdra PT, Timotthy JAD: A further example of a lethal autosomal recessive condition in sibs. J Ment Defic Res 16:139–143, 1972.
Lazjuk GI, Lurie IW, Ostrowskaja TI, et al.: Brief clinical observations: the Neu-Laxova syndrome—a distinct entity. Am J Med Genet 3:261–267, 1979.
Meguid NA, Temtamy SA: Neu-Laxova syndrome in two Egyptian families.
Am J Med Genet 41:30–31, 1991.
Monaco R, Stabile M, Guida F, et al.: Echographic, radiological and anatomo- pathological evaluation of a foetus with Neu-Laxova syndrome. Australas Radiol 36:51–53, 1992.
Mueller RF, Winter RM, Naylor CP: Neu-Laxova syndrome: two further case reports and comments on proposed subclassification. Am J Med Genet 16:645–649, 1983.
Muller LM, de Jong G, Mouton SC, et al.: A case of the Neu-Laxova syndrome:
prenatal ultrasonographic monitoring in the third trimester and the histopathological findings. Am J Med Genet 26:421–429, 1987.
Neu RL, Kajii T, Gardner LI, et al.: A lethal syndrome of microcephaly with multiple congenital anomalies in three siblings. Pediatrics 47:610–612, 1971.
Rode ME, Mennuti MT, Giardine RM, et al.: Early ultrasound diagnosis of Neu-Laxova syndrome. Prenat Diagn 21:575–580, 2001.
Russo R, D’Armiento M, Martinelli P, et al.: Neu-Laxova syndrome: patholog- ical, radiological, and prenatal findings in a stillborn female. Am J Med Genet 32:136–139, 1989.
Scott CI, Louro JM, Laurence KM, et al.: Comments on the Neu-Laxova syn- drome and CAD complex. Am J Med Genet 9:165–175, 1981.
Shapiro I, Borochowitz Z, Degani S, et al.: Neu-Laxova syndrome: prenatal ultrasonographic diagnosis, clinical and pathological studies, and new manifestations. Am J Med Genet 43:602–605, 1992.
Shivarajan MA, Suresh S, Jagadeesh S, et al.: Second trimester diagnosis of Neu Laxova syndrome. Prenat Diagn 23:21–24, 2003.
720 NEU-LAXOVA SYNDROME
Fig. 1. An infant with Neu-Laxova syndrome showing severe ichthyosis, characteristic facial features (absent eyelids, flattened nose, round gaping mouth, low-set ears with poorly developed pin- nae), short broad neck, flexion contractures of the limbs, and short, small-caliber umbilical cord. Photomicrographs of skin (not shown) demonstrated a prominent hyperkeratosis of the epidermis and a thick layer of subcutaneous adipose tissue due to edema.
Fig. 2. Radiographs showing hemivertebrae, kyphoscoliosis and 11 pairs of ribs.
