Congenital midline Abnormalities: About two cases  

Soumeya N Fedala1 , Mahdi A Haddam2 , Farida Chentli1 , Fatima Saraoui1 , Radhia Siyoucef3
1 Service endocrinologie CHU Bab el oued;
2 Service endocrinologie EPH Bologhine Ibn Ziri;
3 Service biochimie Ain naadja hospital
Author    Correspondence author
International Journal of Clinical Case Reports, 2013, Vol. 3, No. 9   doi: 10.5376/ijccr.2013.03.0009
Received: 03 Aug., 2013    Accepted: 05 Aug., 2013    Published: 05 Aug., 2013
© 2013 BioPublisher Publishing Platform
This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Several observations have reported a high frequency (12à50%) of the association between pituitary insufficiency and midline anomalies. The latter are clinical markers that need to systematically search for endocrine disorders. They are hypothalamic origin and are accompanied by abnormalities of the pituitary ontogenesis in 30% of cases. Neuroendocrine disorders and abnormalities of the median line are attached to a embryological defect bud naso frontal primitive that allows the development of different regions of the brain and face. We report two children who had abnormal facial midline. Neuroendocrine and neuroradiological exploration are not made until the appearance of delay stature in one case. Hormonal assessment was in favor of GH deficiency in the first while in the other case the endocrinology consultation was motivated by the existence of a micropenis and cryptorchidism related to hypogonadotropic hypogonadism. There was in both cases a pituitary hypoplasia with other intracranial malformations in one of them. The evolution was marked by the appearance of other hormonal deficiencies. 

Midline abnormalities; Delay stature-failure pituitary-MRI-prenatal ultrasound

1 Introduction
Several observations have reported a high frequency (12à50%) of the association  between  pituitary  insufficiency and  miline  anomalies. They are clinical markers which need systematically to search for endocrine disorders. They have a hypothalamic origin and are accompanied by abnormalities of the pituitary ontogenesis in 30% of cases. Neuroendocrine disorders and anomalies of the median line are attached to an embryological defect bud naso frontal primitive that allows the development of different regions of the brain and face.

2 Observations
2.1 First case
KY, 18 years old, had at birth a typical malformation syndrome midline. But no medical exploration was made until the age of 10  years; the child is oriented to an endocrinology consultation for exploration stature delay. The clinical examination revealed a harmonious dwarfism (Size-4DS / M, -3 DS/TC), a bifid nose, lip and palate slot, crooked teeth, and signs of congenital gonadotropin deficiency with micro penis and bilateral cryptorchidism (Figure 1) . Hormonal balance revealed isolated GH deficiency (Table 1). Gonadal axis has not been explored due to the young age of the subject but magnetic resonance imaging of the hypothalamic pituitary region revealed  pituitary hypoplasia with  voluminous  arachnoid  cyst (Figure 2 and Figure 3) .A correction of  cleft lip slot was made. However, medical treatment with biosynthetic growth hormone is started only eight years later for socio-economic reasons. The evolution was marked by the appearance of secondary  hypothyroidism and insipidus diabetes respectively two and four years after the diagnosis of growth hormone deficiency which necessited substitution. On the stature an accelerated growth rate was observed dice the first year of treatment (+1DS) with a height gain. The size was (-2,5DS/M) after two years of treatment with biosynthetic growth hormone.

Figure 1 KY has a cleft palate, high arched palate, bifid and flattened nose and crooked teeth

Figure 2 A voluminous arachnoid cyst was found during the exploration of short stature associated with abnormalities of the median line in KY

Figure 3 KH has several dysmorphic abnormalities: macrocrania, bifid nose flattened, cleft lip, tongue and bifid uvula, dental malposition Brechet thorax, abdominal adiposity, umbilical hernia, flat feet, hypoplasia of the phalanges, and micropenis anorchidie


Table 1 Hormonal results

2.1 Second case
K.M 1 years and 7 months is hospitalized for exploration a micropenis. He is followed from birth for hydrocephalus. The clinical examination revealed a dysmorphic syndrome that include a macrocrania, a flat nose, cleft lip, a forked tongue, bifid uvula, high-arched palate, dental malposition, a brechet thorax, hypertelorism, umbilical hernia and signs of gonadotropin deficiency: Micropenis with bilateral cryptorchidism (Figure 4).


Figure 4 KM has a congenital anterior pituitary deficit dissociated related syndrome post ectopic pituitary (pituitary hypoplasia (A), interruption of the pituitary stalk (B) and post ectopic pituitary (C))

Hormonal exploration has not objectived of secretory endocrine abnormalities, until the age or the patient has a shift of the curve of growth to 3.5 cm/year .Growth hormone assessment concluded to a growth hormone deficiency (Table 1).   Magnetic resonance imaging of the hypothalamic pituitary region revealed interruption of the pituitary stalk, hypophysis hypoplasia and ectopic post hypophysis. The patient was oriented to maxillofacial surgery for facial correction and  recombinated  growth hormone started.

3 Discussion
Pathologies of the midline are a set of heterogeneous diseases due to abnormal prechordal plate during the fifth week of embryogenesis. They are linked to a primitive embryologic defect bud naso frontal which allows the development of different regions of encephalon and face (Miquel et al., 2005) (Shu et al., 2003). These are rare diseases, which include a wide variety of lesions responsible of psychomotor retardation, convulsion and in some cases a pituitary insufficiency (DeMyer, 1975) (Gupta and Gupta, 2004). These abnormalities usually occur sporadically. Some familial cases have been reported. This syndrome includes anatomical lesions of the middle line of the brain with or without  septo-optic dysplasia (including hypoplasia of the optic nerve and / or pituitary hypoplasia) and facial dysmorphia (Sharma et al., 2012) (Taluant et al., 2011). The pathophysiological of this syndrome remain unknown. However, recent advances in molecular biology have helped to explain a part of this pathology. Genes have been identified in some cases of cleft lip and palate, of holoprosencephaly and Septooptic dysplasia. Other factors such as smoking and taking drugs (anti-epileptics) by the mother during pregnancy may also be responsible for the appearance of a slot (De Meyer, 1964) (Bardeau et al., 1998).

Endocrine abnormalities are frequently associated with the syndrome of the midline. The GH deficiency is the most constant damage (Bardeau et al., 1998). Cerebral magnetic resonance imaging often found malformations as lesions of the hypothalamic pituitary region responsible for more or less complete hypothalamic pituitary insufficiency (Girard et al., 1992) (Coakley et al., 1999) (Sonigo et al., 1988). The existence of an anomaly the median line should be considered as a clinical marker that should systematically consider neuroimaging and neuroendocrine exploration. Hormonal deficiencies should be sought and treated early by opotherapy replacement because in the absence of treatment  vital and  functional prognosis may be compromised. These children may develop acute adrenal insufficiency , somatotropin insufficiency  and hypothyroidism responsible for severe mental retardation and short stature. Close monitoring is recommended for these hormone deficiencies that may not exist at the time of the first endocrine evaluation and appear in the following (Couly and Aicardi, 1988) (Bardeau et al., 1998).

The role of imaging is essential in the management of this complex disease. It can detect malformations injuries, conduct a full review in search of other associated anomalies and thus establish a prognosis (Girard et al., 1992).

Currently, thanks to prenatal ultrasound, there is a net decrease in lethal forms and early support in viable forms is assured. Ultrasound is a very important tool for pre and postnatal screening. However, the MRI is more effective and more accurate in analysis of these malformations. It is a crucial component in the prognostic approach to the pathology of the midline (Lair-Milan et al., 1997).

The management  of the midline syndrome is symptomatic and requires a multidisciplinary regular monitoring. The surgical correction has an aesthetic purpose, allowing these children to live with their disability and especially improve the functional prognosis of phonation and nasal ventilation, especially as these children tend to keep the hope of leading a normal life.

The use of a functional rehabilitation and occupational therapy programs may be beneficial.

In fact, the prognosis depends on the severity of the disease. It is  depending on the type, the existence of associated malformations, their syndromic origin or genetic trait.

Prenatal genetic diagnosis and genetic counseling can be offered to families in which a mutation was identified, caution is still appropriate in the dominant forms, because the expression and penetrance can be highly variable.

4 Conclusion
The existence of midline anomalies in children should be considered as a marker and initiate endocrine and neuroradiological investigations as well as a long-term monitoring. The shift in the growth rate, the appearance of signs of hypopituitarism and the existence of hypothalamic pituitary abnormalities makes necessary regular reassessments. Surgical treatment of defects improves the prognosis of these children.

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